bioengineering-10-00076

Citation

  • Kaur, G.; Verma, S.K.; Singh, D.; Singh, N.K. Role of G-Proteins and GPCRs in Cardiovascular Pathologies. Bioengineering 2023, 10, 76.

  • Received: 5 November 2022, Published: 6 January 2023

  • Copyright © 2023 by the authors.

Overview of G-Proteins and GPCRs

  • G-Proteins: Specialized proteins that bind to nucleotides (GTP and GDP); two types: monomeric and heterotrimeric.

  • GPCRs (G-Protein-Coupled Receptors): Transmit signals for various physiological functions and are crucial in cardiovascular pathologies.

Importance of Cardiovascular Diseases (CVDs)

  • CVDs cause significant global morbidity and mortality, accounting for 31% of all deaths (approx. 17.9 million annually).

  • Include disorders like coronary heart disease, myocardial infarction, and stroke.

  • Complex pathophysiology influenced by various cellular processes and intrinsic/extrinsic factors.

G-Proteins Structure and Function

  • Composed of subunits: Gα (stimulatory or inhibitory), Gβ, and Gγ; Gα proteins divided into groups (e.g., Gαs, Gαi).

  • Act as molecular switches; active state (bound with GTP) vs. inactive state (GDP bound).

  • Regulate processes like cell growth, synthesis, and signaling pathways through various downstream effectors.

Role in Cardiovascular Diseases

  • G-proteins are involved in signaling pathways affecting cardiovascular function and disease progression.

  • Heart Failure: Changes in GPCR signaling lead to improper heart response; downregulation of β1 receptors and increased Gi proteins contribute to worsening conditions.

  • Myocardial Ischemia: Imbalance of oxygen supply and demand; GPCRs, particularly adrenergic receptors, play an essential role in this process.

  • Hypertension: The balance between vasoconstrictors and vasodilators is crucial; dysregulation leads to increased blood pressure.

  • Atherosclerosis: Involves receptor interactions and plaque development; G-proteins participate in endothelial dysfunction.

  • Stroke & PAD: G-proteins influence pathways leading to ischemia and vascular remodeling.

Key Mechanisms and Therapies

  • Regulation of GPCR activity via agonists, inverse agonists, and antagonists affects G-protein activation.

  • Potential therapeutic targets in drugs for heart failure, hypertension, and other cardiovascular conditions include GPCR modulators (e.g., β-blockers, ACE inhibitors).

  • Exploration of G-protein signaling in drug development aims to improve specificity and efficacy of treatments.