Functional, Cellular, and Molecular Remodeling of the Heart under Influence of Oxidative Cigarette Tobacco Smoke

Abstract

Passive and active chronic cigarette smoking (CS) remains an international epidemic and a key risk factor for cardiovascular disease (CVD) development. CS-induced cardiac damage is divided into two major and interchangeable mechanisms: (1) direct adverse effects on the myocardium causing smoking cardiomyopathy and (2) indirect effects on the myocardium by fueling comorbidities such as atherosclerotic syndromes and hypertension that eventually damage and remodel the heart. To date, our understanding of cardiac remodeling following acute and chronic smoking exposure is not well elucidated. This manuscript presents for the first time the RIMD (oxidative stress (R), inflammation (I), metabolic impairment (M), and cell death (D)) detrimental cycle concept as a major player in CS-induced CVD risks and direct cardiac injury. Breakthroughs and latest findings in the field with respect to structural, functional, cellular, and molecular cardiac remodeling following chronic smoking exposure are summarized. This review also touches the genetics/epigenetics of smoking as well as the smoker's paradox and highlights the most currently prominent pharmacological venues to mitigate CS-induced adverse cardiac remodeling.

Figure 1

Vicious and detrimental cycle of CS-induced cardiovascular injury. In addition to exogenous ROS delivery, chronic smoking exposure attenuates antioxidant defenses and increases endogenous ROS formation. Oxidative stress (R) will eventually trigger an inflammatory response (I) and metabolic impairment (M) and subsequent cell death (D) that fuel ROS formation. This chronic phenomenon could lead to CVD. The presence of CVD exacerbates CS-mediated RMID process detrimental effects.

Figure 2

The impact of chronic smoking exposure on CVD risk and cardiac structural, functional, and cellular damage. CS-based RMID cause metabolic and cellular damages that alter cardiac structure and function and increase CVD risk and myocardial damage. HR, heart rate; BP, blood pressure; LV, left ventricle; LVM, left ventricular mass; LA, left atria; LVEDD, left ventricular end-diastolic diameter; LVESD, left ventricular end-systolic diameter; LVEDV, left ventricular end-diastolic volume; LVEF, left ventricular ejection fraction; LVFS, left ventricular fractional shortening; ROS, reactive oxygen species; NOX, NADPH oxidase; GSSG, glutathione disulfide; GSH/GSSH, glutathione disulfide/glutathione ratio; SOD, superoxide dismutase; GSH-px, glutathione peroxidase; eNOS, endothelial nitric oxide synthases; PGI₂, prostacyclin; LDH, lactate dehydrogenase; [Ca²⁺]_m, mitochondrial calcium; MPT, mitochondrial permeability transition; NF-κb, nuclear factor-κB; FA, fatty acid; DAMPs, danger-associated molecular patterns.