Background Diabetes mellitus is associated with coronary dysfunction, contributing to a 2- to 4-fold increase in the risk of coronary heart diseases. The mechanisms by which diabetes induces vasculopathy involve endot...Background Diabetes mellitus is associated with coronary dysfunction, contributing to a 2- to 4-fold increase in the risk of coronary heart diseases. The mechanisms by which diabetes induces vasculopathy involve endothelial-dependent and -independent vascular dysfunction in both type 1 and type 2 diabetes mellitus. The purpose of this study is to determine the role of vascular large conductance Ca2＋-activated K＋ （BK） channel activities in coronary dysfunction in streptozotocin-induced diabetic rats. Methods Using videomicroscopy, immunoblotting, fluorescent assay and patch clamp techniques, we investigated the coronary BK channel activities and BK channel-mediated coronary vasoreactivity in streptozotocin-induced diabetic rats. Results BK currents （defined as the iberiotoxin-sensitive K＋ component） contribute （65＋4）% of the total K＋currents in freshly isolated coronary smooth muscle cells and 〉50% of the contraction of the inner diameter of coronary arteries from normal rats. However, BK current density is remarkably reduced in coronary smooth muscle cells of streptozotocin-induced diabetic rats, leading to an increase in coronary artery tension. BK channel activity in response to free Ca2＋ iS impaired in diabetic rats. Moreover, cytoplasmic application of DHS-1 （a specific BK channel i~ subunit activator） robustly enhanced the open probability of BK channels in coronary smooth muscle cells of normal rats. In diabetic rats, the DHS-1 effect was diminished in the presence of 200 nmol/L Ca2＋ and was significantly attenuated in the presence of high free calcium concentration, i.e., 1 μmol/L Ca2＋. Immunoblotting experiments confirmed that there was a 2-fold decrease in BK-β1 protein expression in diabetic vessels, without alterinq the BK channel a-subunit expression.Although the cytosolic Ca2＋ concentration of coronary arterial smooth muscle cells was increased from （103±23） nmol/L （n=5） of control rats to （193±22） nmol/L （n=6, P 〈0.05） of STZ-induced diabetic展开更多
Objective： Coronary artery calcification （CAC） is thought to be a controlled metabolic process that is very similar to the formation of new bone. In patients with chronic renal failure （CRF）, CAC is very common, ...Objective： Coronary artery calcification （CAC） is thought to be a controlled metabolic process that is very similar to the formation of new bone. In patients with chronic renal failure （CRF）, CAC is very common, and CAC severity correlates with the deterioration of renal lilnction. We summarized the current understanding and emerging findings of the relationship between CAC and CRF. Data Sources： All studies were identified by systematically searching PubMed, Embase, and CNKI databases for the terms ＂coronary calcification＂, ＂＇chronic renal failure＂, ＇~vascular smooth muscle cell＂, and their synonyms until September 2017. Study Selection： We examined the titles and abstracts of all studies that met our search strategy thoroughly. The full text of relevant studies was evaluated. Reference lists of retrieved articles were also scrutinized for the additional relevant studies. Results： CRF can accelerate CAC progression. CRF increases the expression of pro-inflamrnatory factors, electrolyte imbalance （e.g., of calcium, phosphorus）, parathyroid hon^none, and uremic toxins and their ability to promote calcification. These factors, through the relevant signaling pathways, trigger vascular smooth muscle cells to transtbrm into osteoblast-like cells while inhibiting the reduction of vascular calcification factors, thus inducing further CAC. Conclusions： Coronary heart disease in patients with CRF is due to multiple factors. Understanding the mechanism of CAC can help interventionists to protect the myocardium and reduce the prevalence of coronary heart disease and mortality.展开更多
Objective To investigate the preventive effect of magnetic stent on coronary restenosis after percutaneous arterial stenting. Methods Twenty rabbits were divided randomly into 2 groups.Bare stent (BS group,n=10) or ma...Objective To investigate the preventive effect of magnetic stent on coronary restenosis after percutaneous arterial stenting. Methods Twenty rabbits were divided randomly into 2 groups.Bare stent (BS group,n=10) or magnetic stent (MS group,n=10) was implanted in the left iliac artery of the rabbits of the 2 groups,respectively.Aspirin (25rag,qd) was administered orally to the rabbits of both groups from 3 days before stenting until the rabbits were executed.Unfractionated heparin (2500u,qd) was delivered subcuta- neously after stenting for 7 days.Five rabbits of each group were randomly selected to be executed at 7 or 30 days.Structural changes in the injured arteries were studied by optical microscopey,transmissive electronic microscopey and immunohistochemistry.Results At 7 days,more myofibroblasts were found migrating from adventitia to tunica media and intima in BS group than in MS group.Inside the media and intima,large amount of smooth muscle cells of synthetic type were observed.At 30 days after stenting,in magnetic group, most uascular smooth muscle cells (SMCs) under the intima had transformed to contractile type and only little extracellular matrix (ECM) was observed around the SMCs;whereas,in BS group,the SMCs remained to be synthetic type and large amount of ECM was observed around the SMCs,which was composed mainly ofproteoglycans and glycoproteins.Conclusions Magnetic stent can inhibit proliferation and migration of SMCs and reducing the production of ECM,and therefore,may prevent restenosis after coronary stenting.展开更多
基金the National Natural Science Foundation of China，Natural Science Foundation of Jiangsu Province，Medical Key Personnel of Jiangsu Province，Top Qualified Personnel in Six Fields of Jiangsu Province (006) to WANG Ru-xing and the American Diabetes Association Junior Faculty Awards
文摘Background Diabetes mellitus is associated with coronary dysfunction, contributing to a 2- to 4-fold increase in the risk of coronary heart diseases. The mechanisms by which diabetes induces vasculopathy involve endothelial-dependent and -independent vascular dysfunction in both type 1 and type 2 diabetes mellitus. The purpose of this study is to determine the role of vascular large conductance Ca2＋-activated K＋ （BK） channel activities in coronary dysfunction in streptozotocin-induced diabetic rats. Methods Using videomicroscopy, immunoblotting, fluorescent assay and patch clamp techniques, we investigated the coronary BK channel activities and BK channel-mediated coronary vasoreactivity in streptozotocin-induced diabetic rats. Results BK currents （defined as the iberiotoxin-sensitive K＋ component） contribute （65＋4）% of the total K＋currents in freshly isolated coronary smooth muscle cells and 〉50% of the contraction of the inner diameter of coronary arteries from normal rats. However, BK current density is remarkably reduced in coronary smooth muscle cells of streptozotocin-induced diabetic rats, leading to an increase in coronary artery tension. BK channel activity in response to free Ca2＋ iS impaired in diabetic rats. Moreover, cytoplasmic application of DHS-1 （a specific BK channel i~ subunit activator） robustly enhanced the open probability of BK channels in coronary smooth muscle cells of normal rats. In diabetic rats, the DHS-1 effect was diminished in the presence of 200 nmol/L Ca2＋ and was significantly attenuated in the presence of high free calcium concentration, i.e., 1 μmol/L Ca2＋. Immunoblotting experiments confirmed that there was a 2-fold decrease in BK-β1 protein expression in diabetic vessels, without alterinq the BK channel a-subunit expression.Although the cytosolic Ca2＋ concentration of coronary arterial smooth muscle cells was increased from （103±23） nmol/L （n=5） of control rats to （193±22） nmol/L （n=6, P 〈0.05） of STZ-induced diabetic
基金This study was supported by a grant from the National Natural Science Foundation of China （No. 81573732）.
文摘Objective： Coronary artery calcification （CAC） is thought to be a controlled metabolic process that is very similar to the formation of new bone. In patients with chronic renal failure （CRF）, CAC is very common, and CAC severity correlates with the deterioration of renal lilnction. We summarized the current understanding and emerging findings of the relationship between CAC and CRF. Data Sources： All studies were identified by systematically searching PubMed, Embase, and CNKI databases for the terms ＂coronary calcification＂, ＂＇chronic renal failure＂, ＇~vascular smooth muscle cell＂, and their synonyms until September 2017. Study Selection： We examined the titles and abstracts of all studies that met our search strategy thoroughly. The full text of relevant studies was evaluated. Reference lists of retrieved articles were also scrutinized for the additional relevant studies. Results： CRF can accelerate CAC progression. CRF increases the expression of pro-inflamrnatory factors, electrolyte imbalance （e.g., of calcium, phosphorus）, parathyroid hon^none, and uremic toxins and their ability to promote calcification. These factors, through the relevant signaling pathways, trigger vascular smooth muscle cells to transtbrm into osteoblast-like cells while inhibiting the reduction of vascular calcification factors, thus inducing further CAC. Conclusions： Coronary heart disease in patients with CRF is due to multiple factors. Understanding the mechanism of CAC can help interventionists to protect the myocardium and reduce the prevalence of coronary heart disease and mortality.
文摘Objective To investigate the preventive effect of magnetic stent on coronary restenosis after percutaneous arterial stenting. Methods Twenty rabbits were divided randomly into 2 groups.Bare stent (BS group,n=10) or magnetic stent (MS group,n=10) was implanted in the left iliac artery of the rabbits of the 2 groups,respectively.Aspirin (25rag,qd) was administered orally to the rabbits of both groups from 3 days before stenting until the rabbits were executed.Unfractionated heparin (2500u,qd) was delivered subcuta- neously after stenting for 7 days.Five rabbits of each group were randomly selected to be executed at 7 or 30 days.Structural changes in the injured arteries were studied by optical microscopey,transmissive electronic microscopey and immunohistochemistry.Results At 7 days,more myofibroblasts were found migrating from adventitia to tunica media and intima in BS group than in MS group.Inside the media and intima,large amount of smooth muscle cells of synthetic type were observed.At 30 days after stenting,in magnetic group, most uascular smooth muscle cells (SMCs) under the intima had transformed to contractile type and only little extracellular matrix (ECM) was observed around the SMCs;whereas,in BS group,the SMCs remained to be synthetic type and large amount of ECM was observed around the SMCs,which was composed mainly ofproteoglycans and glycoproteins.Conclusions Magnetic stent can inhibit proliferation and migration of SMCs and reducing the production of ECM,and therefore,may prevent restenosis after coronary stenting.
