Cell signalling in the cardiovascular system: an overview

Abstract

Cells must be able to monitor and respond appropriately to changes in their extracellular environment, a process that is often termed “stimulus-response coupling”. Signal transduction (cell signalling) systems allow cells to detect changes in their extracellular milieu and to mount appropriate responses. Although numerous types of receptor systems have evolved to detect extracellular stimuli, the family of receptors that transmit signals through the activation of heterotrimeric GTP binding proteins (G proteins) are important in many different tissues and play prominent roles in cells and tissues of the cardiovascular system. These proteins represent the largest group of cell surface receptors encoded by the mammalian genome (> 1% of human genes), and in the cardiovascular system G protein coupled receptors (GPCRs) are implicated in more or less every regulatory event. Thus, signalling through GPCRs regulates the degree of peripheral arterial resistance, aspects of renal function, the rate and force of myocardial contraction, and cardiac hypertrophy.¹ GPCRs involved in normal cardiovascular function include those that respond to angiotensin II (AT₁ receptors), to endothelin-1 (ET_1B receptors), and to epinephrine and norepinephrine (α and β adrenergic receptors). These receptors are expressed on cardiac myocytes, vascular smooth muscle cells (VSMC) and endothelial cells, and signalling through them orchestrates the normal physiological control of vascular tone, heart rate, and contractility. Moreover, since angiotensin II, endothelin-1, and adrenergic agonists promote the growth of cardiomyocytes, stimulate vascular smooth muscle cell (VSMC) proliferation, and modify endothelial cell function, signalling through their receptors can also contribute to the pathological changes exemplified by excessive cardiac hypertrophy, atherosclerosis, and hypertension.