Mutations in phosphodiesterase 3A ( PDE3A ) Cause Hypertension Without Cardiac Damage.
Maria ErcuStephan WalterAnastasiia SholokhPublished in: Hypertension (Dallas, Tex. : 1979) (2023)
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.
Keyphrases
- blood pressure
- hypertensive patients
- heart rate
- cell proliferation
- smooth muscle
- left ventricular
- oxidative stress
- heart failure
- gene expression
- newly diagnosed
- type diabetes
- transcription factor
- end stage renal disease
- binding protein
- high glucose
- arterial hypertension
- genome wide
- pi k akt
- cell cycle
- adipose tissue
- single molecule
- combination therapy