Therapeutic potential of gasotransmitters for cold stress-related cardiovascular disease

Abstract

Growing evidence has shown that exposure to low ambient temperature poses a huge challenge to human health globally. Actually, cold stress is closely associated with a higher incidence of cardiovascular morbidity and mortality in winter or in cold regions. Cellular and molecular mechanisms underlying cardiovascular complications in response to cold exposure have yet to be fully clarified. Considering that cold exposure is an important risk of cardiovascular complications, it is necessary to clarify the molecular mechanism of cold stress-induced cardiovascular diseases and to develop effective intervention strategies. Hydrogen sulfide (H2S), nitric oxide (NO), and carbon monoxide (CO) are well-known gasotransmitters that are endogenously produced in many biological systems. Accumulating studies have demonstrated that these gasotransmitters play a critical role in a wide spectrum of physiological and/or pathophysiological processes by regulating numerous signaling pathways. These gas signal molecules are emerging as important players in cardiovascular homeostasis, and disruption of these gasotransmitters is critically implicated in cardiovascular anomalies, such as hypertension, atherosclerosis, myocardial ischemia, heart failure, and stroke. Also, evidence is emerging that H2S, NO, and CO may be involved in the pathologies of cold stress-induced cardiovascular ailments. In this review, we aim to highlight and discuss the recent advances towards the development of gasotransmitters-based therapeutics for cold stress-related cardiovascular pathogenesis. We believe that the effects of H2S, NO, and CO on cardiovascular regulation under cold environment will attract tremendous interest in the near future as they serve as novel regulators of cardiovascular biology in cold environment.

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“…Consequently, H2S has emerged as a promising candidate for protection against cardiovascular disease, since physiologic concentrations of H 2 S can exert effects on mitochondrial function and promote myocardial cell survival [8,9]. Given the multi-factorial impact of H 2 S on processes associated with cardiovascular pathophysiology, such as anti-inflammatory, anti-oxidative, and anti-apoptotic actions, some research studies have focused on the potential application of gasotransmitterderived interventions in the treatment and prevention of coldinduced cardiovascular diseases [10,11]. Wei et al conducted both in vivo and in vitro experiments to examine the cardioprotective effect of H 2 S in a rat model.…”