Mutations in phosphodiesterase 3A (PDE3A) cause hypertension without cardiac damage

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Item Type:	Review
Title:	Mutations in phosphodiesterase 3A (PDE3A) cause hypertension without cardiac damage
Creators Name:	Ercu, M., Walter, S. and Klussmann, E.
Abstract:	Hypertension with brachydactyly (HTNB) represents an autosomal dominant form of hypertension. It is a rare syndrome, in which the blood pressure can rise by more than 50 mmHg. If untreated, the patients die of stroke by the age of 50 years. In HTNB, vascular smooth muscle cell proliferation is increased, vasodilation compromised, and the kidney not affected. Surprisingly, after decades of hypertension, HTNB is not associated with hypertension-induced cardiac damage. HTNB is caused by gain-of-function mutations in the phosphodiesterase 3A (PDE3A) gene. The mutant enzymes are hyperactive. PDE3A (phosphodiesterase 3A) hydrolyzes and thereby terminates cyclic adenosine monophosphate signaling in defined cellular compartments. The cardioprotective effect involves local changes of cyclic adenosine monophosphate signaling and inhibition of Ca(2+) reuptake into the sarcoplasmic reticulum of cardiac myocytes. This review introduces HTNB and discusses how insight into the molecular mechanisms underlying HTNB could contribute to a better understanding of blood pressure control and lead to PDE3A-directed strategies for the treatment of essential hypertension and the prevention of hypertension-induced cardiac damage. A focus will be on cAMP (cyclic adenosine monophosphate) signaling compartments.
Keywords:	Cardiac Hypertrophy, Heart Failure, Hypertension, Genetics, Phosphodiesterase
Source:	Hypertension
ISSN:	0194-911X
Publisher:	American Heart Association
Volume:	80
Number:	6
Page Range:	1171-1179
Date:	June 2023
Official Publication:	https://doi.org/10.1161/hypertensionaha.122.19433
PubMed:	View item in PubMed

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