Calcineurin inhibition, cardiovascular consequences, vascular resistance, and potential responses

Item Type:	Review
Title:	Calcineurin inhibition, cardiovascular consequences, vascular resistance, and potential responses
Creators Name:	Luft, F.C.
Abstract:	AIM: To place the consequences of calcineurin inhibition in a cardiovascular context. METHODS: Literature review coupled with personal encounters. RESULTS: Calcineurin is a calcium-binding and calmodulin-binding protein that is conserved across evolution from yeast to mammals. The enzyme functions as a calcium-dependent, calmodulin-stimulated protein phosphatase. Its role in regulating physiology has largely been elucidated by observing calcineurin inhibition. Calcineurin inhibition transformed organ transplantation from an experiment into a therapy and made much of general immunotherapy possible. The function of this phosphatase and how its inhibition leads to toxicity concern us to this date. Initial research from patients and animal models implicated a panoply of factors contributing to hypertension and vasculopathy. Subsequently, the role of calcineurin in regulating the effective fluid volume, sodium reabsorption, and potassium and hydrogen ion excretion was elucidated by investigating calcineurin inhibition. Understanding the regulatory effects of calcineurin on endothelial and vascular smooth muscle cell function has also made substantial progress. However, precisely how the increase in systemic vascular resistance arises requires further mechanistic research. CONCLUSION: Calcineurin inhibition continues to save lives; however, options to counteract the negative effects of calcineurin inhibition should be vigorously pursued.
Keywords:	Calcineurin, Calcineurin Inhibition, Hypertension, Vasculopathy, Animals, Mammals
Source:	Acta Physiologica
ISSN:	1748-1708
Publisher:	Wiley
Volume:	240
Number:	3
Page Range:	e14084
Date:	March 2024
Official Publication:	https://doi.org/10.1111/apha.14084
PubMed:	View item in PubMed

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