Targeting Smad-Mediated TGFß Pathway in Coronary Artery Bypass Graft

Abstract

Revascularization surgeries such as coronary artery bypass grafting (CABG) are sometimes necessary to manage coronary heart disease (CHD). However, more than half of these surgeries fail within 10 years due to the development of intimal hyperplasia (IH) among others. The cytokine transforming growth factor-beta (TGFß) and its signaling components have been found to be upregulated in diseased or injured vessels, and to promote IH after grafting. Interventions that globally inhibit TGFß in CABG have yielded contrasting outcomes in in vitro and in vivo studies including clinical trials. With advances in molecular biology, it becomes clear that TGFß exhibits both protective and damaging roles, and only specific components such as some Smad-dependent TGFß signaling mediate vascular IH. The activin receptor-like kinase (ALK)-mediated Smad-dependent TGFß signaling pathways have been found to be activated in human vascular smooth muscle cells (VSMCs) following injury and in hyperplastic preimplantation vein grafts. It appears that focused targeting of TGFß pathway constitutes a promising therapeutic target to improve the outcome of CABG. This study dissects the role of TGFß pathway in CABG failure, with particular emphasis on the therapeutic potentials of specific targeting of Smad-dependent and ALK-mediated signaling.

Biomarkers of Inflammation in Predicting the Outcomes of Heart Failure of Ischemic Etiology: the Results of Factor Analysis

“…Трансформирующий фактор роста бета-1 (TGFbeta-1) является прототипом семейства факторов роста и дифференцировки [12]. Существуют доказательства активации данного фактора в поврежденных сосудах после хирургической реваскуляризации миокарда, что способствует развитию гиперплазии интимы трансплантированных сосудов [13]. Одним из членов семейства белков TGF-бета является GDF-15 -фактор роста / дифференцировки 15-го типа.…”

Angiogenesis in hepatocellular carcinoma: mechanisms and anti-angiogenic therapies

“…Endoglin (also known as CD105), a 180 kDa type-1 integral transmembrane glycoprotein, consists of a large extracellular domain, hydrophobic transmembrane domain, and short serine/threonine-rich cytoplasmic tail 32 . CD105 activates the activin receptor-like kinase-1 (ALK1)/SMAD1/5 or ALK4/SMAD2/3 pathways, thereby regulating cell proliferation, migration, extracellular matrix synthesis, and angiogenesis 33 . CD105 exists in both long and short isoforms.…”