Therapeutic Aspects of Carbon Monoxide in Cardiovascular Disease

Abstract

Carbon monoxide (CO) is being increasingly recognized as a potential therapeutic with important signaling functions in various diseases. Carbon monoxide-releasing molecules (CORMs) show anti-apoptotic, anti-inflammatory, and anti-oxidant effects on the tissues of organisms, thus contributing to tissue homeostasis. An increase in reactive oxygen species production from the mitochondria after exposure to CO is also considered one of the underlying mechanisms of cardioprotection, although mitochondrial inhibition is the main toxic mechanism of CO poisoning. This review highlights the mechanism of the biological effects of CO and its potential application as a therapeutic in clinical settings, including in cardiovascular diseases. This review also discusses the obstacles and limitations of using exogenous CO or CORMs as a therapeutic option, with respect to acute CO poisoning.

Keywords: adverse effects; carbon monoxide; cardiovascular diseases; therapeutics.

Figure 1

Schematic diagram of the effects of carbon monoxide on the cardiovascular system. Carbon monoxide (CO) can influence the cardiovascular system through (1) the vasodilatory effect, (2) anti-apoptotic activity, and (3) immune-modulation mechanisms. The roles of CO in the cardiovascular system may be executed in conjunction with other gasotransmitters, such as nitric oxide (NO) and hydrogen sulfide (H₂S). The possibility of action on the cardiovascular system is represented by the dotted line. The upward pointing arrow and the downward pointing arrow mean activation and inhibition for each pathway, respectively.

Figure 2

Mechanisms of the favorable effects of carbon monoxide in cardiovascular diseases. Carbon monoxide (CO) can exhibit inhibitory effects on the initiation and progression of cardiovascular disease. (1) CO could suppress the formation of atherosclerosis in the coronary artery and prevent the initiation of coronary artery obstructive disease by the inhibition of the proliferation of smooth muscle cells in the coronary artery. (2) Through anti-apoptotic and anti-inflammatory properties, CO could diminish the loss of myocyte following acute coronary syndrome. (3) The vasodilatory effects of CO can prevent the vicious cycle of heart failure by inhibiting vasoconstriction as a result of the activated renin/angiotensin system and the sympathetic nervous system to compensate for low cardiac output and systemic hypo-perfusion in heart failure. The upward pointing arrow and the downward pointing arrow mean activation and inhibition for each pathway, respectively.