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 Table of Contents  
Year : 2016  |  Volume : 1  |  Issue : 4  |  Page : 109-117

Ambient particulate matter pollution on lipid peroxidation in cardiovascular diseases

1 Division of Environmental Health Sciences, College of Public Health, Ohio State University, Columbus, Ohio, USA
2 Division of Environmental Health Sciences, College of Public Health; State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China; Davis Heart and Lung Research Institute, College of Medicine, Ohio State University, Columbus, Ohio, USA

Date of Submission23-Nov-2016
Date of Acceptance24-Nov-2016
Date of Web Publication18-Jan-2017

Correspondence Address:
Qinghua Sun
Division of Environmental Health Sciences, College of Public Health, Ohio State University, Columbus, Ohio, USA

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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2468-5690.198616

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Cardiovascular diseases refer to all disorders related to the heart and its circulatory system, such as atherosclerosis, arrhythmia, hypertension, and stroke. In recent years, numerous environmental studies in humans and animal models have confirmed a positive association between ambient particulate matter (PM) exposure and cardiovascular morbidity/mortality. The deleterious impacts of the exposure are involved in multiple mechanisms, in which one is due to the pro-inflammatory effects that result from the peroxidation of lipids, which provide critical structure and function in cellular membranes, the main sites of pollutant attack. This review aims to assess the current scientific literature relating to pertinent mechanisms, molecular pathways, and at-risk populations associated with cardiovascular complications induced by ambient PM exposure.

Keywords: Ambient particulate matter pollution, cardiovascular diseases, lipid peroxidation

How to cite this article:
Ulintz L, Sun Q. Ambient particulate matter pollution on lipid peroxidation in cardiovascular diseases. Environ Dis 2016;1:109-17

How to cite this URL:
Ulintz L, Sun Q. Ambient particulate matter pollution on lipid peroxidation in cardiovascular diseases. Environ Dis [serial online] 2016 [cited 2023 May 31];1:109-17. Available from: http://www.environmentmed.org/text.asp?2016/1/4/109/198616

  Introduction Top

Particulate matter (PM) exposure is a risk factor for cause-specific cardiovascular diseases (CVDs) morbidity and mortality, which can potentially lead to a series of related complications. PM is a complex composed of acids such as nitrates and sulfates, organic chemicals, liquid droplets, metals, and soil or dust particles. PM is most commonly discovered in haze, typically emitted by traffic pollution, power plants, and forest fires. [1] The three types of PM researchers are commonly focused on are named based on their aerodynamic diameters, including coarse (<10 μm; PM 10 ), fine (<2.5 μm; PM 2.5 ), and ultrafine (<0.1 μm; PM 0.1 ) particles. Exposure to PM 10 has been demonstrated positively associated with inflammation, endothelial dysfunction, elevated systolic blood pressure, increased atherogenicity of low-density lipoprotein (LDL), and reduced high-density lipoprotein (HDL) cholesterol, in addition to other various cardiovascular complications. [2],[3] The mechanism of the effects on CVD is hypothesized to be a result of many factors, including a combined oxidative insult from PM itself, the stimulation of enzymes that generate reactive oxygen species (ROS) in the vascular endothelium, and through activation of inflammatory cells and neurohumoral pathways. Researchers are unsure as to what extent PM-induced oxidative stress is a direct consequence of inhaled particles and to what extent it is just an outcome of disease progression; however, free radical pathways have been strongly linked to the cardiovascular effects of air pollution. [2],[3] Furthermore, local and systemic oxidative stress as a result of lipid oxidation have been linked to the relationship between PM exposure and CVD. Lipid oxidation is the process by which free radicals take electrons from lipids (typically LDL) in the cell, which is the first step in mutagenic substance formation in the body. These air pollutants cause oxidative mutations of plasma lipoproteins, decreasing the protective effects of HDL and increasing the atherogenicity of LDL, as plasma HDL protects endothelial cells from apoptosis and intracellular ROS generated by oxidized LDL. [4] High concentrations of LDL in relation to low concentrations of HDL can lead to vascular endothelium dysfunction among other serious complications in high-risk populations. [5]

  Endothelial dysfunction Top

Irregular inflammatory pathways and responses play a key role in aggravating CVD. To maintain a regulated and highly functional inflammatory response, a stimulated endothelium must be present with adhesive molecules for white blood cells. [6] The vascular endothelium is a monolayer of cells lining the veins and arteries and is located on the intima between the vascular smooth muscle cells and vessel lumen. The endothelium maintains vascular homeostasis by regulating vasoconstriction, vasodilation, thrombosis, inflammation, and platelet build-up while serving as a selectively permeable barrier between blood and tissue. [7] Cell type-specific agonists for monocytes, neutrophils, and lymphocytes must also be generated by the endothelium, and their role is to excite adherent cells that receive both adhesion- and agonist-related stimuli from vascular endothelial cells. [6] Oxidation of lipid components on the plasma membrane is detrimental to the vessel wall as high concentrations of oxidized lipids are atherogenic and can induce blood vessel damage to the reaction process while provoking plaque build-up in the arteries. [8] Furthermore, oxidized LDL directly damages endothelial cells, and antioxidants such as B-carotene or Vitamin E are extremely important to the elimination of these deleterious effects. Recent studies proved that omega-3 fatty acid supplements or aspirin could protect against the adverse effects associated with PM exposure. [9],[10] In spontaneous hypertensive rat model with exposure to residual oil fly ash, the rats exhibited exacerbated pulmonary injury, an attenuated antioxidant response, and acute depression in ST segment area of electrocardiogram, which is consistent with a greater susceptibility to adverse health effects of fugitive combustion PM. [11] Furthermore, serum paraoxonase, which is found in HDL, may inhibit LDL oxidation and protect against atherosclerosis. A lack of serum paraoxonase promotes LDL oxidation and in turn atherosclerosis. [12] In addition to the harmful effects of oxidized LDL, a lack of nitric oxide (NO) in the endothelium as a result of oxidative stress can also be detrimental. NO is synthesized from the amino acid L-arginine in the endothelial cells by the enzyme NO synthase (NOS) that catalyzes NO synthesis. [13] The proper functioning of the endothelium depends on NOS pathway. NO signals cellular activities, helps to relax the vascular smooth muscles of the vessel, and regulates vasodilation. In the NOS enzyme system, L-arginine is a key substrate by which endogenous NOS (eNOS) produces NO, but it is typically reduced in availability in regard to vascular diseases. High levels of asymmetric dimethylarginine, a naturally occurring product of metabolism as a result of oxidative stress and competitive inhibitor of L-arginine, further inhibit NO levels. Furthermore, when electrochemically uncoupled, NOS becomes a generator of superoxide, which can provoke a chain reaction leaving the entire system dysfunctional. Phosphorylation by cellular kinases (the addition of a phosphate group to a molecule) can also modify eNOS activity by turning certain protein enzymes on and off. [14] NO mediates vascular homeostasis, which includes moderation of local cell growth and protection of the vessel itself, preventing cell adhesion and platelet aggression by interacting with prostacyclin to produce antiatherogenic and thromboresistant effects. [15] NOx-derived enzymes also play a role in regulating smooth muscle cell growth, maintaining proper function of vascular smooth muscle cells, responding to inflammatory stress, and stimulating activity of matrix metalloproteinase, a group of enzymes responsible for tissue reparation. A lack of NO in the endothelium can lead to a lack of such maintenance. [16],[17] When faced with the absence of NO in the endothelium, vasoconstrictors that trigger unwanted cell proliferation and growth such as endothelin-1 and angiotensin II can be activated. In addition, angiotensin-converting enzyme inhibitors reduce the inactivation of bradykinin, which helps stimulate NO release [Figure 1]. [18] In light of these findings, studies have proven that patients with cardiovascular risk who were treated with angiotensin-converting enzyme inhibitors experienced a significant decrease in blood pressure. [19] In addition to angiotensin-converting enzyme inhibitors, studies show that increasing adiponectin (APN) levels may improve endothelial function in patients. Adiponectin is a protein involved with regulating glucose levels and lipid metabolism and breaking down fatty acids. To ascertain the relationship between plasma levels of APN and endothelial dysfunction, wild-type mice and APN knockout type mice were compared. Endothelial dependent and independent vasodilators induced similar concentration-dependent vascular relaxation in the vascular rings of wild-type mice. However, a reduced response was observed with the addition of endothelial-dependent vasodilators when observing the APN mice's vascular rings, which may be important to consider when treating patients experiencing endothelial dysfunction. [20] A recent study conducted in healthy, nonsmoking, young adults in Utah found that episodic PM 2.5 exposures were associated with increased endothelial cell apoptosis, an antiangiogenic plasma profile, and elevated levels of circulating monocytes and T, but not B, lymphocytes, which could contribute to the pathogenic sequelae of atherogenesis and acute coronary events. [21]
Figure 1: Endothelium dysfunction and nitric oxide reduction in the presence of oxidative stress and the asymmetric dimethylarginine inhibitor. (A) Exposure to particulate matter leads to an increase in plasma membrane nicotinamide adenine dinucleotide phosphate activity. Nicotinamide adenine dinucleotide phosphate oxidase transfers electrons from nicotinamide adenine dinucleotide phosphate to molecular oxygen, which produces an excess of reactive oxygen species superoxide anion radicals in the cell, leading to the production of antioxidants. (B) Oxidative stress provokes intracellular Ca2 +‑mediated events in the cell, which further activates additional production of reactive oxygen species such as superoxide anion radicals and nitric oxide. These byproducts come together to form peroxynitrite, a potent oxidant. (C and D) Being a Ca2+‑dependent enzyme, endogenous nitric oxide synthase activity is catalyzed and increases nitric oxide synthesis. Peroxynitrite oxidizes tetrahydrobiopterin, decreasing tetrahydrobiopterin levels, and tetrahydrobiopterin reduction partially uncouples endogenous nitric oxide synthase, causing endothelium oxidative damage. (E) The substrate L‑arginine is a key in producing nitric oxide but is typically reduced in availability in the subjects with cardiovascular diseases. High levels of asymmetric dimethylarginine, a product of metabolism as a result of oxidative stress, a competitive inhibitor of L‑arginine, limit the ability of nitric oxide to bind to L‑arginine

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The effects of PM exposure on major endothelial dysfunction in both human and animal studies are summarized in [Table 1].
Table 1: Endothelial dysfunction

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  Reactive oxygen species and lipid oxidation Top

Lipid peroxidation, in the simplest terms, is a process under which oxidants such as free radicals attack lipids that contain carbon-carbon double bonds, especially polyunsaturated fatty acids containing two or more double bonds. This is because the C-H London dispersion bonds on either side of a carbon double bond are the weakest bonds in a fatty acid chain if the fatty acid is esterified in a complex phospholipid. Cellular membranes are the primary sites of pollutant attack, and lipids provide structure and function to these membranes. Inflammation produces the enzymes that can trigger lipid oxidation by generating a series of reactive oxidants to interact with the C-H bond. [6] The lipid oxidation typically involves oxygen insertion and hydrogen extraction from a carbon chain, resulting in the removal of electrons from a lipid. These electrons are then added to other molecules to generate energy, which is how free radicals are formed. As bonds rearrange and molecular oxygen is adducted, the molecular is made to be quite vulnerable and unstable, causing excessive reaction products as a result of oxidative attack. [22] These actions produce the generation of lipid peroxyl radicals such as hydroperoxyl radical. The hydroperoxyl radical has the ability to yield hydrogen peroxide, which can react with redox-active metals to form hydroxyl radicals with a propensity toward attacking biomolecules and inflicting oxidative stress upon cells. Hydroperoxyl radicals have the potential to provoke a systemic oxidation of polyunsaturated phospholipids and severely impair membrane function. When the body cannot keep up with oxidation, it represses proteins that are supposed to regulate inflammatory pathways and lessens the cell storage of antioxidants [Figure 2]. [23],[24]
Figure 2: Initiation and propagation of lipid peroxidation. (A) Oxidized lipids can be formed in the presence of oxygen free radicals, as the double bonds of polyunsaturated fatty acids are vulnerable to attack by reactive oxygen species. (B and C) When the presence of a double bond weakens an adjacent carbon‑hydrogen bond, oxygen free radicals are able to extract H + from methylene carbons, causing the lipid to become a free radical (L•−). (D and E) The lipid radicals then react with oxygen to form a peroxyl radical (LOO•+). (F‑I) The reaction is self‑propagating as the new radical is an unstable molecule and continues to react easily with oxygen. The peroxyl radical then extracts H + from adjacent lipids to form lipid hydroperoxides and more radical products; if not terminated quickly enough, there will be critical damage to the cell membrane

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In addition, ROS and redox signaling play a key role in the oxidation of HDL/LDL and the inactivation of NO in the endothelium. ROS are formed as a response to the metabolism of oxygen and have a key function in maintaining homeostasis. However, there needs to be a balance between ROS generation and enzymatic systems that overly accelerate or reduce ROS concentrations to maintain internal homeostasis within the body. [25] Free radical-induced oxidation damages macromolecules, cell membranes, and DNA and provokes accelerated cell death known as apoptosis. Excessive ROS production has the potential to change cell phenotype and cell functions through covalent modification as well as inactivate NO. [15]

Potential ROS sources in the human body include mitochondria, plasma membranes, and endoplasmic reticulum. It is important to note that mitochondria are the main source of ROS. In a 2013 study, inflammation biomarkers such as interleukin (IL)-6, C-reactive protein (CRP), and tumor necrosis factor (TNF)-α were observed after exposure to a variety of different air pollutants. [26] Air pollutants tested included NO, carbon monoxide (CO), organic carbon, elemental and black carbon (BC), and PM mass. PM was analyzed and extracted to identify the presence of polycyclic aromatic hydrocarbons (PAHs). IL-6 and TNF-α were associated with the pollutants CO, NO, BC, and PAH, as well as with oxidative potential of ultrafine PM. The associations were stronger for haplogroup H, which was a protective factor against systemic inflammation in this study, and should be paid close attention to follow-up studies. [26] Mitochondrial haplogroup H is related to high ROS production and oxidative stress-induced inflammation, while mitochondrial haplogroup U is related to low ROS production [Figure 3]. [26]
Figure 3: Potential sources of lipid oxidation in the human body. (A) Nicotinamide adenine dinucleotide phosphate oxidase is reactive to stimulation from angiotensin II, thrombin, and endothelin‑1, which occurs as a result of oxidative stress. Nicotinamide adenine dinucleotide phosphate oxidase‑derived superoxide inactivates of nitric oxide to form peroxynitrite, leading to impaired endothelium‑dependent vasodilation and uncoupling of endogenous nitric oxide synthase to form additional superoxide. (B) Enzyme systems such as cytochrome p450 also contribute to the inactivation
of nitric oxide, leading to superoxide formation. (C and D) Reactive oxygen species damages macromolecules, cell membranes, and DNA, causing accelerated cell death. Excessive reactive oxygen species production can change cell phenotype and cell functions via covalent modification and inactivate nitric oxide. (E and F) Reactive oxygen species has been shown to function like signaling molecules in enzymes systems do, provoking intercellular adhesion molecule‑1 and vascular cell adhesion molecule‑1 expressions, which contain binding sites for the molecules and mediate leukocyte adhesion to the endothelium during inflammation. This contributes to the inactivation of nitric oxide and leads to superoxide formation

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Enzyme systems such as lipoxygenase, cyclooxygenase, and cytochrome p450, a probable source of endothelium-derived hyperpolarizing factor, may also be important sources of and contribute to the inactivation of NO. [27] It has also been shown that ROS may functions like signaling molecules do, triggering intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 expressions, which contain binding sites for the molecules and mediate leukocyte adhesion to the endothelium during inflammation. This is achieved by turning on the ERK/AKT/NF-κB-dependent inflammatory pathways, further provoking monocyte adhesion to endothelial cells [Table 2]. [28] Endothelial cell adhesion molecules are upregulated in the vascular endothelium when stimulated by inflammation. This then mediates leukocyte recruitment and endothelium function at the early stages of vascular inflammation. In a recent study, vistafin was also found to be a vascular inflammatory molecule that increases the expression of inflammatory biomarker cell adhesion molecules: ICAM-1 and VCAM-1 through ROS-dependent NF-kB activation in endothelial cells. [32]
Table 2: Reactive oxygen species and nicotinamide adenine dinucleotide phosphate oxidase in cardiovascular disease

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  Nicotinamide adenine dinucleotide phosphate oxidase and its role in cardiovascular diseases Top

Present in the endothelium, nicotinamide adenine dinucleotide phosphate (NAD[P]H) oxidase contains gp91phox, which is reactive to stimulation from angiotensin II, thrombin, and endothelin-1 that occurs as a result of oxidative stress. NAD(P)H oxidase-derived superoxide inactivates NO to form peroxynitrite, which leads to impaired endothelium-dependent vasodilation and uncoupling of eNOS, and in turn, the formation of additional superoxide. [17] NAD(P)H activity is also stimulated in organisms with CVD - elevated levels of this activation can be observed in myocardial cells of humans with CVD and in ischemia-reperfusion models. This is partially due to the activation of angiotensin II as a result of oxidative stress, which in turn stimulates NAD(P)H oxidase. In a rabbit model of early atherosclerosis, where hypercholesterolemia was provoked by inducing a defect in LDL-receptors, it was shown that NAD(P)H-induced ROS production was twice as large when comparing the disease group to the controls. [33] Furthermore, to explore the mechanistic pathways by which PM 2.5 influences inflammatory exposure, a mouse model showed that chronic exposure to ambient PM 2.5 provoked an influx in oxidized phospholipids in the lungs that caused a heightened inflammatory defense through Toll-like receptor (TLR4)/NAD(P)H oxidase-dependent mechanisms. It also appeared that TLR4 activation is necessary for NAD(P)H oxidase activation as TLR4 and gp91phox deficiency prevented NAD(P)H oxidase activation. [29] In addition, to examine the proposition that inhaled concentrated ambient PM (CAPs) promote atherosclerosis through induction of vascular ROS and reactive nitrogen species, mice were exposed to CAPs of PM 2.5 . It was discovered that the composite plaque area of the thoracic aorta had grown significantly with prominent macrophage infiltration and lipid deposition and therefore concluded that CAPs exposure in urban areas enhances atherosclerosis though NAP (P) H oxidase-dependent pathways. [30] Moreover, a study that aimed to examine the role of early life exposure of PM 2.5 proved that contact with high levels is a risk factor for inflammation, adiposity, and insulin resistance in wild-type C57BL/6 mice. After exposure to PM 2.5 for 10 weeks, abnormalities observed in these mice included increased macrophage infiltration in visceral adipose tissue, vascular dysfunction, and enlarged subcutaneous and visceral fat contents. However, ROS generation by NAD(P)H oxidase was shown to reduce this risk [Table 2]. [31]

  Other deleterious impacts Top

PM has also been shown to accelerate plaque build-up in the circulatory system. To understand the pathophysiological pathways that correlate PM with cardiovascular complications, populations of three different groups were examined - nonsmokers with type 2 diabetes, nonsmokers with impaired glucose tolerance, and nonsmokers with genetic predispositions that had the potential to affect inflammatory pathways. Blood panels were analyzed for CRP, IL-6, soluble CD40 ligand (sCD40 L), fibrinogen, myeloperoxidase, and plasminogen activator inhibitor (PAI)-1 to observe the associations between PM and these biomarkers. Small positive correlations were observed between the panel with the patients having genetic susceptibility and fibrinogen, while sCD40 L, PAI-1, and IL-6 were decreased in association with the presence of air pollution. No significant results were observed within the other two populations, but the group with the genetic susceptibility showed an apparent inverse correlation between blood biomarkers and PM pollution, which may increase inflammation and complications involving atherosclerotic diseases. [34] Furthermore, many epidemiological studies have proven that components such as PM and carbon (organic) content in PM render fossil fuel gases instigators of cardiovascular complications. Ultrafine particles (UFPs, <0.1 μm) are capable of carrying vast numbers of toxic air pollutants, which render it highly likely that redox-active components will reach the cardiovascular system. High UFPs exposures can cause inflammation of regulatory pathways due to oxidative stress responses, which can aggravate the onset of atherosclerosis, increase blood pressure, increase circulating markers of inflammation and thrombosis, provoke cardiac ischemia and arrhythmias, and inflict myocardial complications. [35] Traffic-related air pollutants are correlated with increased systemic inflammation, increased platelet stimulation, and decreased erythrocyte antioxidant enzyme activity. The components carried by UFPs were found to be very important - primary combustion markers such as elemental and BC, primary organic carbon, CO, nitrogen oxides, and nitrogen dioxide (NO 2 ) were positively correlated with inflammatory biomarkers such as plasma IL-6, soluble platelet selectin, and CRP. However, these inflammatory biomarkers were negatively correlated with erythrocyte antioxidant activity, as shown by the lack of glutathione peroxidase-1 and superoxide dismutase. The smaller the particles were the more strongly they were associated with inflammatory biomarkers. PM <=0.25 was more positively correlated with inflammatory biomarkers than PM 0.25-2.5 . [36] In another study, two biomarkers of systemic inflammation were observed, plasma IL-6 and soluble TNF-α receptor II (sTNF-α-RII). These biomarkers were exposed to indoor and outdoor PM 0.25 . The presence of indoor and outdoor PAHs was positively correlated with the presence of the biomarkers, but organic components and transition metals were not. PAHs are a group of over 100 chemicals that are released from burning organic substances, oil, coal, gasoline, etc., sTNF-RII increased by 135 pH/mL (95% confidence interval [CI]), and IL-6 increased by 0.27 pH/mL (95% CI). This study shows that traffic emission sources of PM 2.5 composed of PAHs were positively associated with biomarkers of systemic inflammation [Table 3]. [37] Not only does oxidative stress caused by PM negatively impact endothelial regulation, but it also has an effect on telomeric erosion as well. Airborne PM is commonly linked to CVD complications by observing the effects of oxidative stress on the body, and the accelerated shortening of telomeres is a key biological pathway by which oxidative stress accelerates age-related morbidity. The shortening of telomeres triggers the quickened progression of diseases such as CVD. The study concludes a link between certain types of PM 2.5 that arise from traffic emissions and accelerated erosion of telomeres may exist, therefore aggravating CVD-related morbidity and mortality. [40]
Table 3: Coagulation and other deleterious impacts

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  Coagulation Top

In a recent study, the underlying mechanisms of increased endothelial cell procoagulant activity were observed following exposure to soluble UFPs. Human coronary artery endothelial cells (HCAECs) were then evaluated based on their ability to stimulate endothelial cell procoagulant activity in platelet-free plasma. It was found that the exposed HCAEC triggered faster fibrin clot formation and early thrombin generation. The UFPs exposure also increased anti-tissue factor (TF) antibody mRNA expression and endothelial H 2 O 2 production, and antioxidants mitigated UFPs-induced upregulation of TF which proved that procoagulant responses could be connected to ROS formation. The study showed that endothelial cell procoagulant activity is triggered by soluble UFPs exposure, and the mechanism provoked involves TF synthesis, ROS production, and NOX-4 enzyme. [38] In many studies, a positive association between PM and increased coagulation and thrombosis has been identified. Another study aimed to test the relationship between DNA gene methylation, which is the process that a methyl group is added to the cytosine or adenine nucleotides, and PM-induced hypercoagulability. Coagulation activation is increased in association with PM 10 , PM with a diameter of 1 μm (PM 1 ), and zinc. NOS-3 methylation was negatively associated with PM 10 , PM 1 , zinc, and iron exposures. Zinc exposure was negatively correlated with endothelin-1 (EDN 1 ) methylation. Lower NOS 3 and EDN 1 were associated with higher endogenous thrombin potential, which proves that NOS 3 and EDN 1 hypomethylation are of the mechanisms for PM-induced coagulation effects [Table 3]. [39]

  Susceptible populations and clinical studies Top

Across a wide range of studies, healthy subjects did not exhibit high stress responses in exposure to PM when compared to individuals with a history of CVD complications. People with healthy, clean coronaries are not at a heightened risk to short-term particulate exposure, but in patients with underlying coronary artery disease, short-term particulate exposures contributed to acute coronary complications. [41] In a 2015 study related to heart rate variability (HRV), PM 2.5 was associated with root-mean square of successive differences (r-MSSD), but stronger correlations were observed with BC, an indicator of the presence of PM as a result of traffic pollution. Secondary particles were more weakly associated with r-MSSD as was ozone (O 3 ). No associations were seen with sulfur dioxide (SO 2 ) or NO 2 . CO had similar patterns of the association to BC, which was disappeared after controlling for BC. The evidence in this study indicated that BC had a substantially higher effect on standard deviation of normal RR intervals in the individuals who had a previous myocardial infarction. [42] Epidemiological relationships between at-risk populations in relation to CVD and PM exposure have also been extensively analyzed. Among individuals with chronic diseases, health service use was increased with higher levels of exposure to air pollution, as measured by the Air Quality Health Index. [43] In a recent study regarding the effects on pulmonary system such as changes in overall blood chemistry, NO 2 concentrations typically had to exist above 1-2 parts per matter for significant effects on at-risk patients to be observed. It was found that healthy individuals exposed to NO 2 levels below 1 ppm typically did not exhibit cardiovascular complications. This atmospheric concentration usually is not reached outdoors, but within the home, gas cooking can cause it to range between 0.4 and 1.5 ppm. Therefore, a good guideline NO 2 level for susceptible populations was ascertained to be between 0.2 and 0.6 ppm. [44]

Reducing exposure to household air pollution from biomass fuel use is an opportunity for cardiovascular prevention as biomass fuel use has been associated with a higher likelihood of having hypertension and high blood pressure. [45] Looking outside of the home, it is also important to note that extreme weather has been shown to increase risk of heart attacks and other cardiovascular ailments when combined with PM pollution, and a decline in particle pollution levels has been linked to longer life expectancy. [46] A recent study conducted in 24 healthy young adults in Shanghai, China, further demonstrated that short-term wearing of particulate-filtering respirators was associated with a decrease of 2.7 mmHg in systolic blood pressure and increases of HRV parameters in a randomized crossover trial. [47] One particular study observing the seasonal variation of the effects of air pollution on blood pressure during July-September showed that PM 10 and NO 2 concentrations were strongly correlated with elevated blood pressure. During October-December, however, correlations between PM 10 and NO 2 with elevated blood pressure did not exist. Instead, elevated blood pressure was significantly associated with SO 2 and O 3 concentrations. The results of this particular study show that susceptibility is heightened during the summer months. [48] Furthermore, studies have also indicated strong associations between PM 2.5 and arterial vasoconstriction. A particular study of 24 healthy adults showed a mean decrease of 0.09 mm in brachial artery diameter when exposed to PM 2.5 , as opposed to a mean constriction of 0.01 mm in those exposed to filtered air. [49] A clear, defined relationship exists between PM 2.5 and subclinical atherosclerosis, determined by measuring carotid intima-media thickness in the veins and arteries. [50] In addition, a recent cohort study of 114,537 women indicated that women with diabetes were most susceptible to the negative effects of PM on CVD. There was also a positive correlation of higher risks among women over 70 years of age, obese women, and women living in the Northeast and Southern US. [51] Further regarding the susceptibility of women to the deleterious effects of PM, in one particular study, levels of PM 2.5 exposure varied from 3.4 to 28.3 μg/m 3 (mean, 13.5) during each test. Each increase of 10 μg/m 3 was associated with a 24% increase in the risk of a cardiovascular event and a 76% increase in the risk of death from CVD in postmenopausal women. [52] Although low socioeconomic status and inadequate access to treatments and medications for CVD are positively correlated, there was no evidence of synergistic effects of higher PM 2.5 and adverse social/psychosocial factors on blood pressure. In contrast, there was weak evidence of stronger associations of with blood pressure in higher socioeconomic status groups. [53] The population and clinical studies are summarized in [Table 4].
Table 4: Population and clinical studies

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  Conclusion Top

The review of this literature has concentrated largely on the pervasive influence of air pollution on lipid peroxidation and its effects on cardiovascular-related complications. Experimental studies have shown ambient PM exposure increases risk for arteriosclerosis, arrhythmia, coronary artery disease, coagulation, hypertension, and stroke, and the aggravation of these ailments is correlated with inflammatory and oxidative effects that persist as a result of PM exposure. Moving forward, focus should be directed toward evaluating the risks and benefits of using statin therapy in test subjects from a wide array of socioeconomic, cultural, and ethnic backgrounds, as well as furthering exploring the degree of risk that the elderly, those with a genetic predisposition to cardiovascular complications, and individuals living in urban areas experience in their daily lives as a result of PM exposure. There is much still unknown about the toxicology of ambient PM, the mechanistic pathways responsible for provoking adverse cardiovascular health effects in humans, and the gene susceptibility that at-risk individuals may demonstrate, and further research is necessary to minimize the risk that PM poses to global public health.

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