Abstract
Cardiovascular diseases (CVD), especially acute myocardial infarction, are the leading cause of death, morbidity and disability across the world, affecting millions of people each year. Atherosclerosis (AS) is the major cause of CVD, and is a chronic inflammation involving different cell types and various molecular mechanisms. Ca2+ dynamics of endothelial cells (ECs) and smooth muscle cells (SMCs) exert a significant influence on many aspects of CVD. Transient receptor potential channel 5 (TRPC5) is a member of the transient receptor potential (TRP) channels, which consists of a large number of nonselective cation channels with variable degrees of Ca2+-permeability. As a Ca2+-permeable cation channel, Human TRPC5 is expressed in a number of cell types, including ECs and muscle cells, as well as lungs and kidneys. TRPC5 is involved in renal, tumorous, neuronal and vascular diseases. In recent years, the roles of TRPC5 in CVD have been widely implicated in various disorders, such as AS, cardiac hypertrophy and blood pressure regulation. The TRPC5 mechanism of action may be associated with regulation of calcium homeostasis, oxidative stress and apoptosis. In this review, we highlight the significant roles of TRPC5 in the heart, and evaluate the potential of therapeutics targets which block TRPC5 for the treatment of CVD and related diseases.
Highlights
Cardiovascular diseases (CVD), especially coronary heart disease (CHD), is associated with high morbidity and mortality worldwide
The transient receptor potential (TRP) family stands for a large team of 28 cation channels fallen into six subfamilies in accordance with their structural homology: TRP canonical (TRPC), TRP melastin (TRPM), TRP vanniloid (TRPV), TRP ankyrin (TRPA), TRP mucolipin (TRPML), and TRP polycystin (TRPP), all of which permeate cations [4]
TRP can be activated by various stimuli, such as thermally-activated channels (TRPV, TRPM or TRPA) and TRPC activated by phospholipase C (PLC)
Summary
CVD, especially coronary heart disease (CHD), is associated with high morbidity and mortality worldwide. Diacylglycerol formed by G protein-coupled receptors (GPCRs)/Gαq/PLC signaling activates TRPC3/6/7, while stretch or depletion of intracellular Ca2+ stores (store-operated Ca2+ entry, SOCE) activates TRPC1/4/5. It appears that most of the isoforms (TRPC1, TRPC3, TRPC4, TRPC5, TRPC6, and TRPC7) are upregulated during chronic cardiac disease in humans and in animal models [8, 9]. TRPC5 expression has been found in a lot of cell types with inheriting mechanosensitive Ca2+ influx, such as ECs, SMCs, cardiac myocytes and arterial baroreceptor neurons [10,11,12,13] It can form channels on its own or assemble with TRPC4. The activation of TRPC5 can be made at the single-channel level if a certain threshold is reached by mechanical stress on the cell [21]
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