Aim: Fluid shear stress is constantly active on vascular wall cells where is responsible for the balance between healthy and atherosclerosis-prone blood vessel. Recently, bone morphogenetic protein-4 (BMP4), a mechanosensitive autocrine cytokine, assumed an important role in the progression of atherosclerosis. The aim of the study was to evaluate in Human Coronary Artery Endothelial (HCAECs) and Smooth Muscle Cells (HCASMCs) how different dynamic conditions of shear stress in presence/absence of Bioresorbable Vascular Scaffold (BVS) and drug influence the expression levels of BMP4 and its specific membrane-bound receptors (BMPR-1a, BMPR-1b, BMPR2). Methods: Primary HCAECs and HCASMCs were both cultured in the manufacturer's recommended medium and between 2nd and 6th passage, were used. Shear stress (1, 10 and 20 dyne/cm2) were chosen and analyzed with/without BVS + Everolimus (600nM). Total RNA was extracted by HCAECs/HCASMCs and BMP4 system was analyzed by Real-Time PCR. Results: The thermal-cycle profile of biomarker and reference gene PCR primers were optimized. The more stable set of reference genes for Real-Time PCR data normalization resulted GAPDH and ACTB. The results related to BMP4 and specific receptors are summarized in table 1.A statistically significant correlation (R2= -0.52, p=0.008) was found in HCAECs between BMP4 and BMPR-2 corroborating its role as principal receptor complex. Conclusions: The balance between BMP4 and its main receptor BMPR-2, evidenced especially in HCAECs with or without BVS, suggests that they may play an important role in the overall control of inflammation and atherosclerosis.
Different dynamic conditions affect the physiological state of endothelial and smooth muscle cells in presence or absence of bioresorbable vascular scaffold via the BMP4 signalling.
Vozzi F;Cabiati M;Pelosi G;
2020
Abstract
Aim: Fluid shear stress is constantly active on vascular wall cells where is responsible for the balance between healthy and atherosclerosis-prone blood vessel. Recently, bone morphogenetic protein-4 (BMP4), a mechanosensitive autocrine cytokine, assumed an important role in the progression of atherosclerosis. The aim of the study was to evaluate in Human Coronary Artery Endothelial (HCAECs) and Smooth Muscle Cells (HCASMCs) how different dynamic conditions of shear stress in presence/absence of Bioresorbable Vascular Scaffold (BVS) and drug influence the expression levels of BMP4 and its specific membrane-bound receptors (BMPR-1a, BMPR-1b, BMPR2). Methods: Primary HCAECs and HCASMCs were both cultured in the manufacturer's recommended medium and between 2nd and 6th passage, were used. Shear stress (1, 10 and 20 dyne/cm2) were chosen and analyzed with/without BVS + Everolimus (600nM). Total RNA was extracted by HCAECs/HCASMCs and BMP4 system was analyzed by Real-Time PCR. Results: The thermal-cycle profile of biomarker and reference gene PCR primers were optimized. The more stable set of reference genes for Real-Time PCR data normalization resulted GAPDH and ACTB. The results related to BMP4 and specific receptors are summarized in table 1.A statistically significant correlation (R2= -0.52, p=0.008) was found in HCAECs between BMP4 and BMPR-2 corroborating its role as principal receptor complex. Conclusions: The balance between BMP4 and its main receptor BMPR-2, evidenced especially in HCAECs with or without BVS, suggests that they may play an important role in the overall control of inflammation and atherosclerosis.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.