Microparticles are small cell vesicles that can be released by almost all eukaryotic cells during cellular stress and cell activation. Within the last 1-2 decades it has been shown that microparticles are useful blood...Microparticles are small cell vesicles that can be released by almost all eukaryotic cells during cellular stress and cell activation. Within the last 1-2 decades it has been shown that microparticles are useful blood surrogate markers for different pathological conditions, such as vascular inflammation, coagulation and tumour diseases. Several studies have investigated the abundance of microparticles of different cellular origins in multiple cardiovascular diseases. It thereby has been shown that microparticles released by platelets, leukocytes and endothelial cells can be found in conditions of endothelial dysfunction, acute and chronic vascular inflammation and hypercoagulation. In addition to their function as surrogate markers, several studies indicate that circulating microparticles can fuse with distinct target cells, such as endothelial cells or leukocyte, and thereby deliver cellular components of their parental cells to the target cells. Hence, microparticles are a novel entity of circulating, paracrine, biological vectors which can influence the phenotype, the function and presumably even the transcriptome of their target cells.This review article aims to give a brief overview about the microparticle biology with a focus on endothelial activation and arterial hypertension. More detailed information about the role of microparticles in pathophysiology and disease can be found in already published work.展开更多
Background Statins improve arterial stiffness in patients with coronary artery disease （CAD）.Hypertension is a predominant contributor of arterial stiffening.However,the influence of hypertension on the effect of st...Background Statins improve arterial stiffness in patients with coronary artery disease （CAD）.Hypertension is a predominant contributor of arterial stiffening.However,the influence of hypertension on the effect of statins for improving arterial stiffness in CAD patients has seldom been investigated.Therefore,in this study,we investigated the relationships between statin use and arterial stiffness in normotensive and hypertensive CAD patients.Methods Brachial-ankle pulse wave velocity （ba-PWV） was measured in 437 patients,including 220 hypertensive CAD patients （121 used statins,99 did not） and 217 normotensive CAD patients （105 used statins,112 did not）.The normotensive and hypertensive CAD patients were matched according to age,sex,and body mass index （BMI）.Results In the normotensive and hypertensive CAD patients,lipid profiles were significantly improved in the statin group compared with the non-statin group.No significant differences in the administered statins （i.e.,atorvastatin,simvastatin,rosuvastatin,and pravastatin） and statin therapy duration were found between normotensive and hypertensive CAD patients （all P＞0.05）.No significant correlation of ba-PWV and statin therapy duration was found in all CAD patients,normotensive CAD patients,or hypertensive CAD patients （all P＞0.05）.ba-PWV in the statin group was significantly lower than that in the non-statin group in normotensive CAD patients （（1331.68±167.52） cm/s vs.（1468.61±244.54） cm/s,P=0.002） but not in hypertensive CAD patients （P＞0.05）.In multiple linear regression analyses,statin therapy was significantly associated with ba-PWV after adjusting for confounding variables in normotensive CAD patients （P=0.018） but not in hypertensive CAD patients （P＞0.05）.Conclusions Statins may significantly improve arterial stiffness in CAD patients,and hypertension may probably influence the effectiveness of statin therapy in improving arterial stiffness in this population.Further studies are required 展开更多
Bone morphogenetic protein 9(BMP9)(or GDF2)was originally identified from fetal mouse liver cDNA libraries.Emerging evidence indicates BMP9 exerts diverse and pleiotropic functions during postnatal development and in ...Bone morphogenetic protein 9(BMP9)(or GDF2)was originally identified from fetal mouse liver cDNA libraries.Emerging evidence indicates BMP9 exerts diverse and pleiotropic functions during postnatal development and in maintaining tissue homeostasis.However,the expression landscape of BMP9 signaling during development and/or in adult tissues remains to be analyzed.Here,we conducted a comprehensive analysis of the expression landscape of BMP9 and its signaling mediators in postnatal mice.By analyzing mouse ENCODE transcriptome datasets we found Bmp9 was highly expressed in the liver and detectable in embryonic brain,adult lungs and adult placenta.We next conducted a comprehensive qPCR analysis of RNAs isolated from major mouse tissues/organs at various ages.We found that Bmp9 was highly expressed in the liver and lung tissues of young adult mice,but decreased in older mice.Interestingly,Bmp9 was only expressed at low to modest levels in developing bones.BMP9-associated TGFβ/BMPR type I receptor Alk1 was highly expressed in the adult lungs.Furthermore,the feedback inhibitor Smads Smad6 and Smad7 were widely expressed in mouse postnatal tissues.However,the BMP signaling antagonist noggin was highly expressed in fat and heart in the older age groups,as well as in kidney,liver and lungs in a biphasic fashion.Thus,our findings indicate that the circulating BMP9 produced in liver and lungs may account for its pleiotropic effects on postnatal tissues/organs although possible roles of BMP9 signaling in liver and lungs remain to be fully understood.展开更多
For many years, it has been recognized that hypertension tends to cluster with various anthropometric and metabolic abnormalities including abdominal obesity, elevated triglycerides, reduced high-density lipoprotein c...For many years, it has been recognized that hypertension tends to cluster with various anthropometric and metabolic abnormalities including abdominal obesity, elevated triglycerides, reduced high-density lipoprotein cholesterol, glucose intolerance, insulin resistance and hyperuricemia. This constellation of various conditions has been transformed from a pathophysiological concept to a clinical entity, which has been defined metabolic syndrome(MetS). The consequences of the MetS have been difficult to assess without commonly accepted criteria to diagnose it. For this reason, on 2009 the International Diabetes Federation, the American Heart Association and other scientific organizations proposed a unified MetS definition. The incidence of the MetS has been increasing worldwide in parallel with an increase in overweight and obesity. The epidemic proportion reached by the MetS represents a major public health challenge, because several lines of evidence showed that the MetS, even without type 2 diabetes, confers an increased risk of cardiovascular morbidity and mortality in different populations including also hypertensive patients. It is likely that the enhanced cardiovascular risk associated with MetS in patients with high blood pressure may be largely mediated through an increased prevalence of preclinical cardiovascular and renal changes, such as left ventricular hypertrophy, early carotid atherosclerosis, impaired aortic elasticity, hypertensive retinopathy and microalbuminuria. Indeed, many reports support this notion, showing that hypertensive patients with MetS exhibit, more often than those without it, these early signs of end organ damage, most of which are recognized as significant independent predictors of adverse cardiovascular outcomes.展开更多
目的通过引入血脂综合指标探讨高血压病患者血脂异常与大动脉僵硬度异常的相关性。方法本研究共纳入高血压病随诊或疑诊动脉粥样硬化相关疾病患者431例。对所有入组患者依据有无高血压病及血脂异常病史分为无高血压病和血脂异常病史组(A...目的通过引入血脂综合指标探讨高血压病患者血脂异常与大动脉僵硬度异常的相关性。方法本研究共纳入高血压病随诊或疑诊动脉粥样硬化相关疾病患者431例。对所有入组患者依据有无高血压病及血脂异常病史分为无高血压病和血脂异常病史组(A组)、有血脂异常病史但无高血压病史组(B组)、有高血压病史但无血脂异常病史组(C组)、有高血压病及血脂异常病史组(D组)。依据总胆固醇(total cholesterol,TC)、甘油三酯(triglyceride, TG)、高密度脂蛋白胆固醇(high density lipoprotein-cholesterol, HDL-C)、低密度脂蛋白胆固醇(low density lipoprotein-cholesterol, LDL-C)等血脂指标分别计算血浆致动脉粥样硬化指数(atherogenic index of plasma,AIP)、非高密度脂蛋白胆固醇(non-high density lipoprotein-cholesterol,non-HDL-C)、TC/HDL-C、动脉硬化指数(atherogenic index,AI)等血脂综合指标,比较各指标组间差异。采用多元线性偏相关分析探讨各血脂指标与肱踝动脉脉搏波传导速度(brachial-ankle pulse wave velocity,baPWV)的相关性。结果 TC、 TG、 HDL-C、AIP、AI、non-HDL-C及TC/HDL-C在各组间总体比较差异均存在统计学意义(均有P<0.05)。针对高血压病患者(C组、D组)进行多元线性偏相关分析,结果显示,TG、HDL-C、AIP、AI、TC/HDL-C与baPWV均呈正相关关系(均有P<0.05),TC、LDL-C、non-HDL-C与baPWV均无明显相关性(均有P>0.05)。结论高血压患者血脂水平与大动脉僵硬度可能存在相关性,AI、AIP及TC/HDL-C等血脂综合指标可能更好反映高血压病患者血脂异常与大动脉僵硬度异常的相关趋势。展开更多
BACKGROUND Pulmonary arterial hypertension(PAH)is a disease of the arterioles resulting in an increased resistance in pulmonary circulation with associated high pressures in the pulmonary arteries,causing irreversible...BACKGROUND Pulmonary arterial hypertension(PAH)is a disease of the arterioles resulting in an increased resistance in pulmonary circulation with associated high pressures in the pulmonary arteries,causing irreversible remodeling of the pulmonary arterial walls.Coronavirus disease 2019(COVID-19)has been associated with development of new onset PAH in the literature leading to symptoms of dyspnea,cough and fatigue that persist in spite of resolution of acute COVID-19 infection.However,the majority of these cases of COVID related PAH were diagnosed using echocardiographic data or via right heart catheterization in mechanically ventilated patients.CASE SUMMARY Our case is the first reported case of COVID related PAH diagnosed by right heart catheterization in a non-mechanically ventilated patient.Right heart catheterization has been the gold standard for diagnosis of pulmonary hypertension.Our patient had right heart catheterization four months after her initial COVID-19 infection due to persistent dyspnea.CONCLUSION This revealed new onset PAH that developed following her infection with COVID-19,an emerging sequela of the infection.展开更多
Resistant hypertension remains a major clinical problem despite the available multidrug therapy.Over the next decades,its incidence will likely increase given that it is strongly associated with older age and obesity....Resistant hypertension remains a major clinical problem despite the available multidrug therapy.Over the next decades,its incidence will likely increase given that it is strongly associated with older age and obesity.Resistant hypertension patients have an increased cardiovascular risk,thus effective antihypertensive treatment will provide substantial health benefits.The crosstalk between sympathetic nervous system and kidneys plays a crucial role in hypertension.It influences several pathophysiological mechanisms such as the central sympathetic tone,the sodium balance and the systemic neurohumoral activation.In fact,studies using several animal models demonstrated that the renal denervation prevented and attenuated hypertension in multiple species.Large reductions in blood pressure were also observed in malignant hypertension patients submitted to sympathectomy surgeries.However,these approaches had an unacceptably high rates of periprocedural complications and disabling adverse events.Recently,an innovative non-pharmacological therapy that modulates sympathetic activation has been successfully developed.Renal sympathetic percutaneous denervation is an endovascular procedure that uses radiofrequency energy to destroy the autonomic renal nerves running inside the adventitia of renal arteries.This method represents a promising new approach to the strategy of inhibiting the sympathetic nervous system.The aim of this review is to examine the background knowledge that resulted in the development of this hypertension treatment and to critically appraise the available clinical evidence.展开更多
Background The reversibility of pulmonary arterial hypertension(PAH)in congenital heart disease(CHD)is of great importance for the operability of CHD.Proteomics analysis found that transgelin was significantly upregul...Background The reversibility of pulmonary arterial hypertension(PAH)in congenital heart disease(CHD)is of great importance for the operability of CHD.Proteomics analysis found that transgelin was significantly upregulated in the lung tissue of CHD-PAH patients,especially in the irreversible group.However,how exactly it participated in CHD-PAH development is unknown.展开更多
文摘Microparticles are small cell vesicles that can be released by almost all eukaryotic cells during cellular stress and cell activation. Within the last 1-2 decades it has been shown that microparticles are useful blood surrogate markers for different pathological conditions, such as vascular inflammation, coagulation and tumour diseases. Several studies have investigated the abundance of microparticles of different cellular origins in multiple cardiovascular diseases. It thereby has been shown that microparticles released by platelets, leukocytes and endothelial cells can be found in conditions of endothelial dysfunction, acute and chronic vascular inflammation and hypercoagulation. In addition to their function as surrogate markers, several studies indicate that circulating microparticles can fuse with distinct target cells, such as endothelial cells or leukocyte, and thereby deliver cellular components of their parental cells to the target cells. Hence, microparticles are a novel entity of circulating, paracrine, biological vectors which can influence the phenotype, the function and presumably even the transcriptome of their target cells.This review article aims to give a brief overview about the microparticle biology with a focus on endothelial activation and arterial hypertension. More detailed information about the role of microparticles in pathophysiology and disease can be found in already published work.
文摘Background Statins improve arterial stiffness in patients with coronary artery disease （CAD）.Hypertension is a predominant contributor of arterial stiffening.However,the influence of hypertension on the effect of statins for improving arterial stiffness in CAD patients has seldom been investigated.Therefore,in this study,we investigated the relationships between statin use and arterial stiffness in normotensive and hypertensive CAD patients.Methods Brachial-ankle pulse wave velocity （ba-PWV） was measured in 437 patients,including 220 hypertensive CAD patients （121 used statins,99 did not） and 217 normotensive CAD patients （105 used statins,112 did not）.The normotensive and hypertensive CAD patients were matched according to age,sex,and body mass index （BMI）.Results In the normotensive and hypertensive CAD patients,lipid profiles were significantly improved in the statin group compared with the non-statin group.No significant differences in the administered statins （i.e.,atorvastatin,simvastatin,rosuvastatin,and pravastatin） and statin therapy duration were found between normotensive and hypertensive CAD patients （all P＞0.05）.No significant correlation of ba-PWV and statin therapy duration was found in all CAD patients,normotensive CAD patients,or hypertensive CAD patients （all P＞0.05）.ba-PWV in the statin group was significantly lower than that in the non-statin group in normotensive CAD patients （（1331.68±167.52） cm/s vs.（1468.61±244.54） cm/s,P=0.002） but not in hypertensive CAD patients （P＞0.05）.In multiple linear regression analyses,statin therapy was significantly associated with ba-PWV after adjusting for confounding variables in normotensive CAD patients （P=0.018） but not in hypertensive CAD patients （P＞0.05）.Conclusions Statins may significantly improve arterial stiffness in CAD patients,and hypertension may probably influence the effectiveness of statin therapy in improving arterial stiffness in this population.Further studies are required
基金The reported work was supported in part by research grants from the National Institutes of Health(CA226303 to TCH)the U.S.Department of Defense(OR130096 to JMW)+3 种基金the Scoliosis Research Society(TCH and MJL)This project was also supported in part by The University of Chicago Cancer Center Support Grant(P30CA014599)the National Center for Advancing Translational Sciences of the National Institutes of Health through Grant Number UL1 TR000430.TCH was also supported by the Mabel Green Myers Research Endowment Fund and The University of Chicago Orthopaedics Alumni Fund.Funding sources were not involved in the study design,in the collection,analysis and interpretation of datain the writing of the report,and in the decision to submit the paper for publication。
文摘Bone morphogenetic protein 9(BMP9)(or GDF2)was originally identified from fetal mouse liver cDNA libraries.Emerging evidence indicates BMP9 exerts diverse and pleiotropic functions during postnatal development and in maintaining tissue homeostasis.However,the expression landscape of BMP9 signaling during development and/or in adult tissues remains to be analyzed.Here,we conducted a comprehensive analysis of the expression landscape of BMP9 and its signaling mediators in postnatal mice.By analyzing mouse ENCODE transcriptome datasets we found Bmp9 was highly expressed in the liver and detectable in embryonic brain,adult lungs and adult placenta.We next conducted a comprehensive qPCR analysis of RNAs isolated from major mouse tissues/organs at various ages.We found that Bmp9 was highly expressed in the liver and lung tissues of young adult mice,but decreased in older mice.Interestingly,Bmp9 was only expressed at low to modest levels in developing bones.BMP9-associated TGFβ/BMPR type I receptor Alk1 was highly expressed in the adult lungs.Furthermore,the feedback inhibitor Smads Smad6 and Smad7 were widely expressed in mouse postnatal tissues.However,the BMP signaling antagonist noggin was highly expressed in fat and heart in the older age groups,as well as in kidney,liver and lungs in a biphasic fashion.Thus,our findings indicate that the circulating BMP9 produced in liver and lungs may account for its pleiotropic effects on postnatal tissues/organs although possible roles of BMP9 signaling in liver and lungs remain to be fully understood.
文摘For many years, it has been recognized that hypertension tends to cluster with various anthropometric and metabolic abnormalities including abdominal obesity, elevated triglycerides, reduced high-density lipoprotein cholesterol, glucose intolerance, insulin resistance and hyperuricemia. This constellation of various conditions has been transformed from a pathophysiological concept to a clinical entity, which has been defined metabolic syndrome(MetS). The consequences of the MetS have been difficult to assess without commonly accepted criteria to diagnose it. For this reason, on 2009 the International Diabetes Federation, the American Heart Association and other scientific organizations proposed a unified MetS definition. The incidence of the MetS has been increasing worldwide in parallel with an increase in overweight and obesity. The epidemic proportion reached by the MetS represents a major public health challenge, because several lines of evidence showed that the MetS, even without type 2 diabetes, confers an increased risk of cardiovascular morbidity and mortality in different populations including also hypertensive patients. It is likely that the enhanced cardiovascular risk associated with MetS in patients with high blood pressure may be largely mediated through an increased prevalence of preclinical cardiovascular and renal changes, such as left ventricular hypertrophy, early carotid atherosclerosis, impaired aortic elasticity, hypertensive retinopathy and microalbuminuria. Indeed, many reports support this notion, showing that hypertensive patients with MetS exhibit, more often than those without it, these early signs of end organ damage, most of which are recognized as significant independent predictors of adverse cardiovascular outcomes.
文摘目的通过引入血脂综合指标探讨高血压病患者血脂异常与大动脉僵硬度异常的相关性。方法本研究共纳入高血压病随诊或疑诊动脉粥样硬化相关疾病患者431例。对所有入组患者依据有无高血压病及血脂异常病史分为无高血压病和血脂异常病史组(A组)、有血脂异常病史但无高血压病史组(B组)、有高血压病史但无血脂异常病史组(C组)、有高血压病及血脂异常病史组(D组)。依据总胆固醇(total cholesterol,TC)、甘油三酯(triglyceride, TG)、高密度脂蛋白胆固醇(high density lipoprotein-cholesterol, HDL-C)、低密度脂蛋白胆固醇(low density lipoprotein-cholesterol, LDL-C)等血脂指标分别计算血浆致动脉粥样硬化指数(atherogenic index of plasma,AIP)、非高密度脂蛋白胆固醇(non-high density lipoprotein-cholesterol,non-HDL-C)、TC/HDL-C、动脉硬化指数(atherogenic index,AI)等血脂综合指标,比较各指标组间差异。采用多元线性偏相关分析探讨各血脂指标与肱踝动脉脉搏波传导速度(brachial-ankle pulse wave velocity,baPWV)的相关性。结果 TC、 TG、 HDL-C、AIP、AI、non-HDL-C及TC/HDL-C在各组间总体比较差异均存在统计学意义(均有P<0.05)。针对高血压病患者(C组、D组)进行多元线性偏相关分析,结果显示,TG、HDL-C、AIP、AI、TC/HDL-C与baPWV均呈正相关关系(均有P<0.05),TC、LDL-C、non-HDL-C与baPWV均无明显相关性(均有P>0.05)。结论高血压患者血脂水平与大动脉僵硬度可能存在相关性,AI、AIP及TC/HDL-C等血脂综合指标可能更好反映高血压病患者血脂异常与大动脉僵硬度异常的相关趋势。
文摘BACKGROUND Pulmonary arterial hypertension(PAH)is a disease of the arterioles resulting in an increased resistance in pulmonary circulation with associated high pressures in the pulmonary arteries,causing irreversible remodeling of the pulmonary arterial walls.Coronavirus disease 2019(COVID-19)has been associated with development of new onset PAH in the literature leading to symptoms of dyspnea,cough and fatigue that persist in spite of resolution of acute COVID-19 infection.However,the majority of these cases of COVID related PAH were diagnosed using echocardiographic data or via right heart catheterization in mechanically ventilated patients.CASE SUMMARY Our case is the first reported case of COVID related PAH diagnosed by right heart catheterization in a non-mechanically ventilated patient.Right heart catheterization has been the gold standard for diagnosis of pulmonary hypertension.Our patient had right heart catheterization four months after her initial COVID-19 infection due to persistent dyspnea.CONCLUSION This revealed new onset PAH that developed following her infection with COVID-19,an emerging sequela of the infection.
文摘Resistant hypertension remains a major clinical problem despite the available multidrug therapy.Over the next decades,its incidence will likely increase given that it is strongly associated with older age and obesity.Resistant hypertension patients have an increased cardiovascular risk,thus effective antihypertensive treatment will provide substantial health benefits.The crosstalk between sympathetic nervous system and kidneys plays a crucial role in hypertension.It influences several pathophysiological mechanisms such as the central sympathetic tone,the sodium balance and the systemic neurohumoral activation.In fact,studies using several animal models demonstrated that the renal denervation prevented and attenuated hypertension in multiple species.Large reductions in blood pressure were also observed in malignant hypertension patients submitted to sympathectomy surgeries.However,these approaches had an unacceptably high rates of periprocedural complications and disabling adverse events.Recently,an innovative non-pharmacological therapy that modulates sympathetic activation has been successfully developed.Renal sympathetic percutaneous denervation is an endovascular procedure that uses radiofrequency energy to destroy the autonomic renal nerves running inside the adventitia of renal arteries.This method represents a promising new approach to the strategy of inhibiting the sympathetic nervous system.The aim of this review is to examine the background knowledge that resulted in the development of this hypertension treatment and to critically appraise the available clinical evidence.
文摘Background The reversibility of pulmonary arterial hypertension(PAH)in congenital heart disease(CHD)is of great importance for the operability of CHD.Proteomics analysis found that transgelin was significantly upregulated in the lung tissue of CHD-PAH patients,especially in the irreversible group.However,how exactly it participated in CHD-PAH development is unknown.
