Targeting G protein‐coupled receptors for heart failure treatment

Abstract

Heart failure remains a leading cause of morbidity and mortality worldwide. Current treatment for patients with heart failure include drugs targeting G protein‐coupled receptors such as β‐adrenoceptor antagonists (β‐blockers) and angiotensin II type 1 receptor antagonists (or angiotensin II receptor blockers). However, many patients progress to advanced heart failure with persistent symptoms, despite treatment with available therapeutics that have been shown to reduce mortality and mortality. GPCR targets currently being explored for the development of novel heart failure therapeutics include adenosine receptor, formyl peptide receptor, relaxin/insulin‐like family peptide receptor, vasopressin receptor, endothelin receptor and the glucagon‐like peptide 1 receptor. Many GPCR drug candidates are limited by insufficient efficacy and/or dose‐limiting unwanted effects. Understanding the current challenges hindering successful clinical translation and the potential to overcome existing limitations will facilitate the future development of novel heart failure therapeutics.

Interaction of Vasopressin with Hormones of the Hypothalamo-Pituitary-Adrenal Axis: Significance for Therapeutic Strategies in Cardiovascular and Metabolic Diseases

“…The AVP receptors belong to a family of G-protein coupled receptors, which includes also receptors for other essential cardiovascular regulators, such as β-agonists, Ang II, endothelin, glucagon-like peptide 1 (GLP-1) and CRH. In high concentrations AVP interacts also with oxytocin receptors [113,[140][141][142][143]. AVPR1a gene has been mapped to the 12q14.2 locus and AVPR1b to the 1q32.1 locus.…”

Role of Ectopic Olfactory Receptors in the Regulation of the Cardiovascular–Kidney–Metabolic Axis

“…In fact, nearly a third of the drugs used for the treatment of cardiovascular disease target GPCRs, with modulators of the adrenergic and angiotensin receptors representing the bulk of the current therapeutic arsenal [5]. In spite of these medical breakthroughs, cardiovascular disease remains a leading cause of morbidity and mortality worldwide, and new pharmacological approaches targeting alternative candidate GPCR pathways are constantly being investigated [6].…”

Cardioprotective effects of Moku-boi-to and its impact on AngII-induced cardiomyocyte hypertrophy

“…Drug therapy is a cornerstone of HF treatment to address this problem. Various drugs targeting G protein-coupled receptors and ion channels are available to prevent the deterioration of ventricular systolic function and reduce mortality in patients (Rahm et al, 2018;Thai et al, 2023). On the other hand, medications used for conditions other than HF, such as antihypertensives and antidiabetic drugs, are prescribed only to people with pre-existing conditions because they can make HF worse (Page et al, 2016).…”