Metabolic Syndrome and Air Pollution: A Narrative Review of Their Cardiopulmonary Effects

Abstract

Particulate matter (PM) exposure and metabolic syndrome (MetSyn) are both significant global health burdens. PM exposure has been implicated in the pathogenesis of MetSyn and cardiopulmonary diseases. Individuals with pre-existing MetSyn may be more susceptible to the detrimental effects of PM exposure. Our aim was to provide a narrative review of MetSyn/PM-induced systemic inflammation in cardiopulmonary disease, with a focus on prior studies of the World Trade Center (WTC)-exposed Fire Department of New York (FDNY). We included studies (1) published within the last 16-years; (2) described the epidemiology of MetSyn, obstructive airway disease (OAD), and vascular disease in PM-exposed individuals; (3) detailed the known mechanisms of PM-induced inflammation, MetSyn and cardiopulmonary disease; and (4) focused on the effects of PM exposure in WTC-exposed FDNY firefighters. Several investigations support that inhalation of PM elicits pulmonary and systemic inflammation resulting in MetSyn and cardiopulmonary disease. Furthermore, individuals with these preexisting conditions are more sensitive to PM exposure-related inflammation, which can exacerbate their conditions and increase their risk for hospitalization and chronic disease. Mechanistic research is required to elucidate biologically plausible therapeutic targets of MetSyn- and PM-induced cardiopulmonary disease.

Keywords: World Trade Center; blood pressure; cardiovascular disease; chronic obstructive pulmonary disease; metabolic syndrome; particulate matter; systemic inflammation.

Figure 1

Schematic of biological mechanisms underlying PM-induced MetSyn, COPD, and CVD. (a) PM- associated Vascular Effects: PM exposure leads to the hypomethylation of TLR4, which may increase systolic blood pressure (SBP) and diastolic blood pressure (DBP), as well as Alu hypomethylation and autonomic imbalance, which may elevate DBP. Increased SBP and DBP contribute to the development of hypertension, a key feature of MetSyn. (b) PM associated MetSyn Phenotype Development: Inhalation of PM elicits the generation of reactive oxygen species (ROS), ER stress, and elevated cytokine levels, such as TNF-α, and IL-6, which in turn activates signal transduction cascades by inducing the activity of cellular kinases (JNK, PKC, IKK). Kinase activation can directly lead to systemic inflammation or do so indirectly by first activating inflammatory pathways (AP-1, NF-κB). (c) PM-associated Lipid Changes (ATX Autotaxin; LPC lysophosphatidylcholine; PLA phospholipase; PAPC 1-palmitoyl-2-arachidonoyl-sn-glycero-3- phosphocholine; SAPC 1-stearoyl-2-arachidonoyl-sn-glycero-phosphocholine; oxLDL oxidized LDL; PA phosphatidic acid). (d) Systemic Inflammation contributes to the development of insulin resistance, abdominal obesity, hypertriglyceridemia, and low HDL, all of which are defining characteristics of MetSyn. (e) MetSyn then increases affected individuals’ risk of developing COPD and CVD. Lines with no arrowhead () indicate enzymatic contribution to downstream catabolic reactions.