Endothelial progenitor cells(EPCs)are a circulating,bone marrow-derived cell population that participate in both vasculogenesis and vascular homeostasis.Recent studies have shown that EPCs are reduced by^50% in diabet...Endothelial progenitor cells(EPCs)are a circulating,bone marrow-derived cell population that participate in both vasculogenesis and vascular homeostasis.Recent studies have shown that EPCs are reduced by^50% in diabetes that correlates inversely with its mortality rate.In addition,EPC angiogenic functions are severely impaired in diabetes.However,the molecular and cellular mechanisms underlying EPC dysfunction are poorly understood.Our current studies have focused on in vitro and in展开更多
Background:Platelet endothelial cell adhesion molecule(PECAM-1)is present in the vascular endothelium and plays important roles in various biological processes.Several recent studies have reported associations between...Background:Platelet endothelial cell adhesion molecule(PECAM-1)is present in the vascular endothelium and plays important roles in various biological processes.Several recent studies have reported associations between PECAM-1 and certain subtypes of cardiovascular diseases(CVDs).However,further research is necessary to clarify the causal effects of PECAM-1 on CVDs.To determine whether PECAM-1 and CVDs are causally associated,we conducted a two-sample Mendelian randomization(TSMR)study.Methods:Single nucleotide polymorphisms(SNPs)associated with PECAM-1 were used as instrumental variants(IVs)to estimate the causal effects of PECAM-1 on CVDs.Six SNPs were included in our TSMR study.The inverse-variance weighted(IVW)method was applied in the primary analysis.To confirm the initial results,we conducted several complementary analyses and pleiotropy analyses.Results:In the IVW analysis,higher genetically predicted PECAM-1 levels were associated with lower risk of coronary artery disease(CAD)(OR,0.835;CI,0.757–0.92;P=3×10-4)and myocardial infarction(MI)(OR,0.79;CI,0.709–0.881;P=2.03×10-5).Conclusions:The findings confirmed that elevated PECAM-1 levels may decrease the risk of CAD and MI.These results confirm the causal effect of PECAM-1 on CVDs and may facilitate further investigation of the mechanism of PECAM-1 in CVD pathogenesis.展开更多
基金Supported by Grants from NIH R01GM077352,VA Merit Award I01RX000244,AHA GIA0855601G,ADA Research Award7-08-RA-23NSFC Overseas Collaborative Grant#30728021
文摘Endothelial progenitor cells(EPCs)are a circulating,bone marrow-derived cell population that participate in both vasculogenesis and vascular homeostasis.Recent studies have shown that EPCs are reduced by^50% in diabetes that correlates inversely with its mortality rate.In addition,EPC angiogenic functions are severely impaired in diabetes.However,the molecular and cellular mechanisms underlying EPC dysfunction are poorly understood.Our current studies have focused on in vitro and in
基金supported by grants from the Ministry of Science and Technology of China(2021YFA0804803 and 2022YFA1104204)National Natural Science Foundation of China(82421001,82230014,81930007,81470389,81500221,81930012,and 82241027)+5 种基金the National Science Fund for Distinguished Young Scholars(81625002)Shanghai Municipal Health Commission(2022JC013,2023ZZ02021,and GWVI-11.1-26)Shanghai Municipal Education Commission(SHSMU-ZDCX20210700)Shanghai Hospital Development Center(SHDC12022102)the Science and Technology Commission of Shanghai Municipality(22JC1402100 and 22DZ2292400)the Major Project of Natural Science Foundation of Hunan Province(Open Competition 2021JC0002).
文摘Background:Platelet endothelial cell adhesion molecule(PECAM-1)is present in the vascular endothelium and plays important roles in various biological processes.Several recent studies have reported associations between PECAM-1 and certain subtypes of cardiovascular diseases(CVDs).However,further research is necessary to clarify the causal effects of PECAM-1 on CVDs.To determine whether PECAM-1 and CVDs are causally associated,we conducted a two-sample Mendelian randomization(TSMR)study.Methods:Single nucleotide polymorphisms(SNPs)associated with PECAM-1 were used as instrumental variants(IVs)to estimate the causal effects of PECAM-1 on CVDs.Six SNPs were included in our TSMR study.The inverse-variance weighted(IVW)method was applied in the primary analysis.To confirm the initial results,we conducted several complementary analyses and pleiotropy analyses.Results:In the IVW analysis,higher genetically predicted PECAM-1 levels were associated with lower risk of coronary artery disease(CAD)(OR,0.835;CI,0.757–0.92;P=3×10-4)and myocardial infarction(MI)(OR,0.79;CI,0.709–0.881;P=2.03×10-5).Conclusions:The findings confirmed that elevated PECAM-1 levels may decrease the risk of CAD and MI.These results confirm the causal effect of PECAM-1 on CVDs and may facilitate further investigation of the mechanism of PECAM-1 in CVD pathogenesis.
