The C2238/αANP Variant Is a Negative Modulator of Both Viability and Function of Coronary Artery Smooth Muscle Cells

摘要: Background: Abnormalities of vascular smooth muscle cells (VSMCs) contribute to development disease. Atrial natriuretic peptide (ANP) exerts important effects on VSMCs. A common ANP molecular variant (T2238C/aANP) has recently emerged as a novel risk factor. Objectives: We aimed at identifying CC2238/aANP viability, migration and motility in coronary artery SMCs, the underlying signaling pathways. Methods Results: Cells were exposed either TT2238/aANP or CC2238/aANP. At end treatment, cell evaluated, along with changes oxidative stress pathway (ROS levels, NADPH eNOS expression), Akt phosphorylation miR21 expression levels. reduced vitality, increased apoptosis necrosis, suppressed consistent its targets (PDCD4, PTEN, Bcl2) phosphorylated As result stress, markedly stimulated contraction. NPR-C gene silencing specific siRNAs restored expression, induced by The cAMP/PKA/CREB pathway, driven activation, significantly contributed both phosphoAkt reduction upon overexpression mimic-hsa-miR21 rescued cellular damage dependent Conclusions: negatively modulates viability through NPR-C/cAMP/PKA/CREB/miR21 it augments leading migratory vasoconstrictor SMCs. These findings further support damaging role this aANP vessel wall potential contribution acute events.