MYPT1 reduction is a novel pathogenic factor of erectile dysfunction

Erectile dysfunction (ED) is closely associated with smooth muscle dysfunction, but its underlying mechanisms remains incompletely understood. We here reported that the reduced expression of myosin phosphatase target subunit 1 (MYPT1), the main regulatory unit of myosin light chain phosphatase, was critical for the development of vasculogenic ED. Male MYPT1 knockout mice had reduced fertility and the penises displayed abolished erections as evidenced by reduced intracavernous pressure (ICP). The penile smooth muscles of the knockout mice displayed enhanced contractility and resistant relaxation. We further identified a natural compound lotusine that increased the MYPT1 expression by inhibiting SIAH1/2 E3 ligases-mediated protein degradation. This compound sufficiently restored the ICP and improved histological characters of the penile artery of Mypt1 haploinsufficiency mice. In diabetic ED mice (db/db), the decreased expression of MYPT1 was measured, and ICP was restored by lotusine treatment. We conclude that the reduction of MYPT1 is the major pathogenic factor of vasculogenic ED. The restoration of MYPT1 by lotusine improved the function of injured penile smooth muscles, and could be a novel strategy for ED therapy.

LONG NON-CODING RNAS AS REGULATORS OF PHYSIOLOGICAL AND PATHOLOGICAL PROCESSES OF THE CARDIOVASCULAR SYSTEM

A large part of the human genome is transcribed into non-coding RNA. This review focuses on long noncoding RNAs (lncRNAs) involved in the regulation of gene expression. We considered information about the molecular mechanisms of of lncRNAs functioning, features of their interaction with miRNAs, mRNAs, DNA and the participation of lncRNAs in physiological and pathological processes of the cardiovascular system. In particular, the review shows the role of lncRNAs in cardiac cell differentiation, ischemic myocardial damage, cardiac hypertrophy, endothelial and smooth muscle dysfunction. Significant changes in the expression of individual lncRNAs in cardiac pathologies allow the use of these molecules for diagnostic purposes and as possible therapeutic targets.

Aneurysmal Dilatation of Ductus Arteriosus and Pulmonary Artery in Association With ACTA2 Mutation

Actin α2 (ACTA2) is a protein crucial for proper functioning of contractile apparatus in smooth muscles. A specific mutation resulting in substitution of arginine at position 179 by histidine (p.R179 H) in ACTA2 has been shown to be associated with multisystemic smooth muscle dysfunction syndrome. Characteristic features include aneurysmal arterial disease. Due to rarity of this disease, we report a nine-year-old girl with this rare genetic variant in whom cardiovascular manifestations were identified in fetal life and who needed neonatal cardiac surgical intervention.