The Na+/K+-ATPase: A potential therapeutic target in cardiometabolic diseases

Abstract

Cardiometabolic diseases (CMD) are a direct consequence of modern living and contribute to the development of multisystem diseases such as cardiovascular diseases and diabetes mellitus (DM). CMD has reached epidemic proportions worldwide. A sodium pump (Na+/K+-ATPase) is found in most eukaryotic cells’ membrane and controls many essential cellular functions directly or indirectly. This ion transporter and its isoforms are important in the pathogenesis of some pathological processes, including CMD. The structure and function of Na+/K+-ATPase, its expression and distribution in tissues, and its interactions with known ligands such as cardiotonic steroids and other suspected endogenous regulators are discussed in this review. In addition, we reviewed recent literature data related to the involvement of Na+/K+-ATPase activity dysfunction in CMD, focusing on the Na+/K+-ATPase as a potential therapeutic target in CMD.

Cytotoxicity and toxicoproteomics analysis of thiazolidinedione exposure in human‐derived cardiomyocytes

“…Our findings revealed significant downregulation of ATPase Na + /K + transporting subunit alpha 1 (ATP1A1), a major component of Na + / K + pump that has a recognisable role in maintaining the electrochemical gradient that arises from the difference in electrical potential and ion concentration across the cell membrane (Obradovic et al, 2023). Hence, dysregulation in ATP1A1 associated with ROSI exposure could have a dramatic effect on the contractile machinery, which could potentially result in elevating cytosolic calcium levels, leading to sustained muscle contraction and, eventually, muscle weakness.…”

Pleiotropic attenuating effect of Ginkgo biloba against isoprenaline-induced myocardial infarction via improving Bcl-2/mTOR/ERK1/2/Na+, K+-ATPase activities

“…In the biopsies of patients with heart failure, for instance, the Na + , K + -ATPase activity was much lower. The aldosterone antagonist was still another factor in the regulation of Na + , K + -ATPase after a heart attack since it lowered hyperaldosteronism and decreased Na + , K + -ATPase activity ( Obradovic et al, 2023 ). In this study, it was found that ISO-exposed animals had decreased cardiac Na + , K + -ATPase activity, which may be related to increased lipid peroxidation and membrane damage.…”

Shenfu injection: a review of pharmacological effects on cardiovascular diseases

“…Na + -K + -ATPase enzyme and Ca 2+ -ATPase enzyme, ubiquitous enzymes in the heart, play a crucial role in process of CVDs ( Fedosova et al, 2021 ). Na + -K + -ATPase transports two Na + ions extrude out of the cell in exchange for one K + ions, thereby maintaining the concentration gradients across the cell membrane ( Fedosova et al, 2021 ; Obradovic et al, 2023 ). Ca 2+ -ATPase, a crucial role for cellular Ca 2+ homeostasis, maintains normal intracellular calcium concentration and prevents calcium overload ( Nguyen et al, 2023 ; Ye et al, 2023 ).…”