Transient Receptor Potential Channels, Natriuretic Peptides, and Angiotensin Receptor-Neprilysin Inhibitors in Patients With Heart Failure

Abstract

Heart failure (HF) remains the leading cause of death, morbidity, and medical expenses worldwide. Treatments for HF with reduced ejection fraction have progressed in recent years; however, acute decompensated heart failure remains difficult to treat. The transient receptor potential (TRP) channel family plays roles in various cardiovascular diseases, responding to neurohormonal and mechanical load stimulation. Thus, TRP channels are promising targets for drug discovery, and many studies have evaluated the roles of TRP channels expressed on pain neurons. The natriuretic peptide (NP) family of proteins regulates blood volume, natriuresis, and vasodilation and can antagonize the renin-angiotensin-aldosterone system and participate in the pathogenesis of major cardiovascular diseases, such as HF, coronary atherosclerotic heart disease, and left ventricular hypertrophy. NPs are degraded by neprilysin, and the blood level of NPs has predictive value in the diagnosis and prognostic stratification of HF. In this review, we discuss the relationships between typical TRP family channels (e.g., transient receptor potential cation channel subfamily V member 1 andTRPV1, transient receptor potential cation channel subfamily C member 6) and the NP system (e.g., atrial NP, B-type NP, and C-type NP) and their respective roles in HF. We also discuss novel drugs introduced for the treatment of HF.

Diagnostic and prognostic significance of miR-320a-3p in patients with chronic heart failure

“…BNP has been recommended by foreign guidelines as a classic indicator of HF clinical diagnosis and efficacy evaluation and is a relatively ideal HF biomarker [ 23 ]. BNP is mainly secreted by ventricular myocytes and has strong diuretic, natriuretic, vasodilator, anti-myocardial fibrosis and other effects [ 24 ]. In the clinical diagnosis of HF, when BNP detection is negative, it can be used to exclude HF.…”

Calcium Homeostasis, Transporters, and Blockers in Health and Diseases of the Cardiovascular System

“…The TRP channel superfamily includes 28 related non-selective anion channels that display different permeability degrees to calcium classified into six subfamilies: canonical (TRPC), vanilloid TRP (TRPV), melastatin TRP (TRPM), ankyrin TRP, mucolipin TRP, and polycystin TRP [121][122][123]. TRPC channels were the first to be cloned and are intensively studied to this day.…”

“…Therefore, the NCX1 isoform is present in the heart and is a plasma membrane protein capable of binding and transporting Na + and Ca 2+ across the plasma membrane [145,146]. Recent evidence also indicates its presence at the levels of mitochondria [119][120][121] and nuclear [16] membranes. It is a crucial Ca 2+ efflux mechanism having an essential role in cytosolic, mitochondrial, and nuclear Ca 2+ regulation.…”

Reduced DNMT1 levels induce cell apoptosis via upregulation of METTL3 in cardiac hypertrophy

“…Cardiac hypertrophy undergoes from concentric to eccentric, resulting in heart fibrosis, enlargement, apoptotic loss of cardiomyocytes, eventually leading to HF which is often fatal [ 3 , 4 ]. Angiotensin II (Ang II), a neurohumoral factor, plays a crucial role in the developmental progression of heart hypertrophy through the activation of intracellular signaling pathways by interacting with membrane receptors, leading to the transcriptional modulation of hypertrophy-related genes [ [5] , [6] , [7] ]. Therefore, further investigation of the molecular mechanisms underlying the action of Ang II will provide a huge advantage in protecting cardiomyocytes from enlargement and cell death during cardiac hypertrophy.…”