1 Introduction Ischemic heart disease is caused by atherosclerotic and/or thrombotic obstruction of coronary arteries. Clinical spec- trum of ischemic heart disease expands from asymptomatic atherosclerosis of corona...1 Introduction Ischemic heart disease is caused by atherosclerotic and/or thrombotic obstruction of coronary arteries. Clinical spec- trum of ischemic heart disease expands from asymptomatic atherosclerosis of coronary arteries to acute coronary syn- dromes （ACS） including unstable angina, acute myocardial infarction （non-ST elevation myocardial infarction and ST elevation myocardial infarction）. Stable ischemic heart dis- ease （SIHD） refers to patients with known or suspected SIHD who have no recent or acute changes in their symp- tomatic status, suggesting no active thrombotic process is underway.展开更多
Vascular smooth muscle cell(VSMC) proliferation and migration are pivotal for the pathogenesis of atherosclerosis and post-angioplasty restenosis. We have recently reported that a disintegrin and metalloproteinase wit...Vascular smooth muscle cell(VSMC) proliferation and migration are pivotal for the pathogenesis of atherosclerosis and post-angioplasty restenosis. We have recently reported that a disintegrin and metalloproteinase with thrombospondin motifs-7(ADAMTS-7), a novel metalloproteinase, contributes directly to neointima formation by mediating VSMC migration. However, whether ADAMTS-7 affects VSMC proliferation remains unclear. In this study, we found that luminal adenoviral delivery of ADAMTS-7 aggravated intimal hyperplasia 7 d after injury, paralleled by an increased percentage of PCNA-positive cells in both intima and media. In contrast, perivascular administration of ADAMTS-7 si RNA, but not scrambled si RNA to injured arteries attenuated intimal thickening at day 7, paralleled with reduced intimal VSMC replication, without alteration of VSMC proliferation in the media. In accordance, [3H]-thymidine incorporation assay in primary cultured rat VSMCs revealed an enhanced replication rate(by 61%) upon ADAMTS-7 overexpression and retarded proliferation(by 23%) upon ADAMTS-7 si RNA administration. Our data demonstrates that ADAMTS-7 promotes VSMC proliferation both in vitro and in vivo. ADAMTS-7 may therefore serve as a novel therapeutic target for atherosclerosis and post-angioplasty restenosis.展开更多
Endothelial cells form the internal barrier between circulating blood and the vessel wall.They regulate arterial activity and mediate pathological reactions to vascular injuries such as atherosclerosis and balloon ang...Endothelial cells form the internal barrier between circulating blood and the vessel wall.They regulate arterial activity and mediate pathological reactions to vascular injuries such as atherosclerosis and balloon angioplasty.The development and differentiation of endothelial cells is a complex and coordinated process involving multiple levels of signaling and transcriptional and post-transcriptional regulation.Elucidating the mechanism of endothelial differentiation will not only enhance our understanding of vascular disease pathogenesis,but also facilitate our ability to produce vessels cells from pluripotent stem cells for regeneration purposes.In this review,we discuss the current understanding of how stem cells differentiate into endothelial cells at the level of signaling,transcription and microRNA regulation.展开更多
文摘1 Introduction Ischemic heart disease is caused by atherosclerotic and/or thrombotic obstruction of coronary arteries. Clinical spec- trum of ischemic heart disease expands from asymptomatic atherosclerosis of coronary arteries to acute coronary syn- dromes （ACS） including unstable angina, acute myocardial infarction （non-ST elevation myocardial infarction and ST elevation myocardial infarction）. Stable ischemic heart dis- ease （SIHD） refers to patients with known or suspected SIHD who have no recent or acute changes in their symp- tomatic status, suggesting no active thrombotic process is underway.
基金supported by funding from the International Cooperation and Exchanges of the National Natural Science Foundation of China(81220108004)the National Basic Research Program of China(2012CB518002)+2 种基金the National Natural Science Foundation of China(81070243,81121061,91339000)the National Science Fund for Distinguished Young Scholars(81225002)Program of Introducing Talents of Discipline to Universities,Ministry of Education of China(B07001)
文摘Vascular smooth muscle cell(VSMC) proliferation and migration are pivotal for the pathogenesis of atherosclerosis and post-angioplasty restenosis. We have recently reported that a disintegrin and metalloproteinase with thrombospondin motifs-7(ADAMTS-7), a novel metalloproteinase, contributes directly to neointima formation by mediating VSMC migration. However, whether ADAMTS-7 affects VSMC proliferation remains unclear. In this study, we found that luminal adenoviral delivery of ADAMTS-7 aggravated intimal hyperplasia 7 d after injury, paralleled by an increased percentage of PCNA-positive cells in both intima and media. In contrast, perivascular administration of ADAMTS-7 si RNA, but not scrambled si RNA to injured arteries attenuated intimal thickening at day 7, paralleled with reduced intimal VSMC replication, without alteration of VSMC proliferation in the media. In accordance, [3H]-thymidine incorporation assay in primary cultured rat VSMCs revealed an enhanced replication rate(by 61%) upon ADAMTS-7 overexpression and retarded proliferation(by 23%) upon ADAMTS-7 si RNA administration. Our data demonstrates that ADAMTS-7 promotes VSMC proliferation both in vitro and in vivo. ADAMTS-7 may therefore serve as a novel therapeutic target for atherosclerosis and post-angioplasty restenosis.
基金supported by the National Natural Science Foundation of China(91339102,81270001,81270180)the Zhejiang Provincial Natural Science Foundation(LR14H020001)
文摘Endothelial cells form the internal barrier between circulating blood and the vessel wall.They regulate arterial activity and mediate pathological reactions to vascular injuries such as atherosclerosis and balloon angioplasty.The development and differentiation of endothelial cells is a complex and coordinated process involving multiple levels of signaling and transcriptional and post-transcriptional regulation.Elucidating the mechanism of endothelial differentiation will not only enhance our understanding of vascular disease pathogenesis,but also facilitate our ability to produce vessels cells from pluripotent stem cells for regeneration purposes.In this review,we discuss the current understanding of how stem cells differentiate into endothelial cells at the level of signaling,transcription and microRNA regulation.
