Particulate Matter Air Pollution: Effects on the Cardiovascular System

Abstract

Air pollution is a complex mixture of gaseous and particulate components, each of which has detrimental effects on human health. While the composition of air pollution varies greatly depending on the source, studies from across the world have consistently shown that air pollution is an important modifiable risk factor for significantly increased morbidity and mortality. Moreover, clinical studies have generally shown a greater impact of particulate matter (PM) air pollution on health than the gaseous components. PM has wide-ranging deleterious effects on human health, particularly on the cardiovascular system. Both acute and chronic exposure to PM air pollution is associated with increased risk of death from cardiovascular diseases including ischemic heart disease, heart failure, and ischemic/thrombotic stroke. Particulate matter has also been shown to be an important endocrine disrupter, contributing to the development of metabolic diseases such as obesity and diabetes mellitus, which themselves are risk factors for cardiovascular disease. While the epidemiological evidence for the deleterious effects of PM air pollution on health is increasingly accepted, newer studies are shedding light on the mechanisms by which PM exerts its toxic effects. A greater understanding of how PM exerts toxic effects on human health is required in order to prevent and minimize the deleterious health effects of this ubiquitous environmental hazard. Air pollution is a growing public health problem and mortality due to air pollution is expected to double by 2050. Here, we review the epidemiological evidence for the cardiovascular effects of PM exposure and discuss current understanding about the biological mechanisms, by which PM exerts toxic effects on cardiovascular system to induce cardiovascular disease.

Keywords: cardiovascular; coagulation; inflammation; interleukin-6; lung; macrophage; particulate matter; thrombosis.

Figure 1

Current evidence for the mechanisms by which particulate matter air pollution causes cardiovascular health effects. Exposure Level: PM exposure is hypothesized to exert its effects on the cardiovascular system by three routes: (1) PM induces an inflammatory response in the lung. PM acts on the cells of the lung, including alveolar macrophages, leading to mitochondrial reactive oxygen species (mROS)-dependent pro-inflammatory cytokine production. (2) Inhaled PM acts on sensory receptors in the lung, promoting activation of the hypothalamic pituitary adrenal (HPA) axis and sympathetic pathway activation in the autonomic nervous system (ANS). (3) Other effects of PM exposure may be mediated by translocation of particles into the circulatory system, or by particle ingestion, which may promote inflammation in the gut. Signaling Level: Cytokines produced into the lung “spillover” into the circulation, leading to a systemic state of inflammation. Translocated particles as well as inflammation resulting from particle injection may also contribute to a general state of systemic inflammation. Sympathetic activation leads to elevated levels of circulating catecholamines. Subclinical Level: Systemic inflammation and elevated catecholamine levels act on target cells leading to acute phase response, hypercoagulable state (activation of coagulation, and suppressed fibrinolysis), vasoconstriction, increased blood pressure, cardiac electrical changes, endothelial dysfunction, and increased adiposity and insulin resistance complicated by adipose tissue inflammation. Elevated catecholamine levels due to ANS imbalance further increase inflammation. Sympathetic activation leads to increased catecholamine production, which increases heart rate and promotes vasoconstriction, endothelial dysfunction, and hypertension. Clinical Level: The combined effects of systemic inflammation and sympathetic activation on their cellular targets lead to the clinical effects of PM on cardiovascular disease. These effects are seen at both the acute level (acute ischemic/thrombotic events, cardiac arrhythmias, or acute heart failure), or at the chronic level (atherosclerosis, hypertension, and chronic heart failure).