Microcirculation最新文献_第5页

Men with nonobstructive coronary disease have higher burden of ischemic heart disease detected by cardiopulmonary exercise test 通过心肺运动测试发现，患有非阻塞性冠状动脉疾病的男性患缺血性心脏病的比例更高

IF 2.4 4区医学 Q3 HEMATOLOGY

Microcirculation

Pub Date : 2024-01-17 DOI: 10.1111/micc.12841

Siyuan Li, Yifang Yuan, Lanting Zhao, Tingting Lv, Fei She, Fang Liu, Yajun Xue, Boda Zhou, Ying Xie, Yu Geng, Ping Zhang

Background

Nonobstructive coronary artery disease (NOCAD), characterized by the presence of myocardial ischemic symptoms and signs without obstructive coronaries, is a common clinical condition, but it is less well understood. Few studies have analyzed the gender differences in inducible myocardial ischemia assessed by cardiopulmonary exercise test (CPET) in NOCAD.

Methods

We conducted a study of 289 NOCAD patients (mean age 60, 56% women) with ischemic symptoms and confirmed ⫹50% coronaries stenoses by coronary angiography who underwent symptom-limited CPET. We assessed ischemic response using predicted % peak VO₂, O₂ pulse trajectory, and exercise ECG test.

Results

Men with NOCAD had significantly lower predicted % peak VO₂ (62% vs. 73%), higher proportions of flattening pattern (16% vs. 2%), and downward patterns of O₂ pulse trajectory (2% vs. 0%) (p < .0001) compared with women. In contrast, women with NOCAD had a higher prevalence of shallow patterns of O₂ pulse trajectory (21% vs. 6%, p < .0001). Men with NOCAD had a higher risk ischemic profile (medium risk: 63% vs. 54%, high risk: 18% vs. 4%, p < .0001). After adjustment, men with NOCAD had significantly lower predicted % peak VO₂ (β −27.4, 95% CI −30.74 to −24.07), higher risk for abnormal O₂ pulse trajectories (OR 4.21, 95% CI 1.93 to 9.19), and myocardial ischemia risk per CPET parameters (OR 3.14, 95% CI 1.78 to 5.54) (p < .0001).

Conclusion

Men with NOCAD had a higher risk profile for ischemic heart disease per CPET. Therefore, they should receive rigorous management and follow-up to prevent cardiovascular events.

非阻塞性冠状动脉疾病（NOCAD）的特征是存在心肌缺血症状和体征，但没有阻塞性冠状动脉，这是一种常见的临床病症，但人们对它的了解较少。很少有研究分析了通过心肺运动测试（CPET）评估非阻塞性冠心病诱发性心肌缺血的性别差异。

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引用次数: 0

Coronary microvascular dysfunction as assessed by multimodal diagnostic imaging in patients with hypertrophic cardiomyopathy is related to the severity of cardiac dysfunction 通过多模式诊断成像评估肥厚型心肌病患者的冠状动脉微血管功能障碍与心功能不全的严重程度有关。

IF 2.4 4区医学 Q3 HEMATOLOGY

Microcirculation

Pub Date : 2024-01-04 DOI: 10.1111/micc.12843

Tien Vuong Tran, Loic Djaileb, Laurent Riou, Lea Ruez Lantuejoul, Joris Giai, Gilles Barone-Rochette

Introduction

Coronary microvascular dysfunction (CMD) plays a major role in hypertrophic cardiomyopathy (HCM) physiopathology but its assessment in clinical practice remains a challenge. Nowadays, innovations in invasive and noninvasive coronary evaluation using multimodal imaging provide options for the diagnosis of CMD. The objective of the present study was to investigate if new multimodal imaging diagnosis of CMD could detect HCM patients with more impaired cardiac function by left atrioventricular coupling index (LACI).

Methods and Results

A total of 32 consecutive patients with a confirmed diagnosis of HCM (62 ± 13 years, 62% men) were prospectively screened for CMD using a multimodal imaging method. LACI was assessed by cardiovascular magnetic resonance imaging. Fifteen (47%) patients had CMD by multimodal imaging method. Patients with CMD presented a significantly higher LACI (48.5 ± 25.4 vs. 32.5 ± 10.6, p = .03). A multivariate logistic regression analysis demonstrated that CMD was independently associated with LACI (OR = 1.069, 95% CI 1.00–1.135, p = .03).

Conclusion

Multimodal imaging diagnosis of CMD is applicable to HCM patients and is associated with more impaired cardiac function.

导言：冠状动脉微血管功能障碍（CMD）在肥厚型心肌病（HCM）的生理病理中起着重要作用，但在临床实践中对其进行评估仍是一项挑战。如今，利用多模态成像技术进行有创和无创冠状动脉评估的创新为 CMD 的诊断提供了选择。本研究旨在探讨新的 CMD 多模态成像诊断是否能通过左房室耦合指数（LACI）发现心功能受损更严重的 HCM 患者：采用多模态成像方法对连续确诊为 HCM 的 32 名患者（62 ± 13 岁，62% 为男性）进行了 CMD 前瞻性筛查。心血管磁共振成像对 LACI 进行了评估。通过多模态成像方法，15 名（47%）患者患有 CMD。CMD患者的LACI明显更高（48.5 ± 25.4 vs. 32.5 ± 10.6，p = .03）。多变量逻辑回归分析表明，CMD与LACI独立相关（OR = 1.069，95% CI 1.00-1.135，p = .03）：结论：CMD 的多模态成像诊断适用于 HCM 患者，且与心功能受损程度更严重相关。

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引用次数: 0

Nitric oxide-mediated vasodilation in human bone 一氧化氮介导的人体骨骼血管扩张。

IF 2.4 4区医学 Q3 HEMATOLOGY

Microcirculation

Pub Date : 2023-12-22 DOI: 10.1111/micc.12842

Adina E. Draghici, Matthew R. Ely, Jason W. Hamner, J. Andrew Taylor

Objective

Regulation of blood flow to bone is critical but poorly understood, particularly in humans. This study aims to determine whether nitric oxide (NO), a major regulator of vascular tone to other tissues, contributes also to the regulation of blood flow to bone.

Methods

In young healthy adults (n = 16, 8F, 8M), we characterized NO-mediated vasodilation in the tibia in response to sublingual nitroglycerin and contrasted it to lower leg. Blood flow responses were assessed in supine individuals by continuously measuring tibial total hemoglobin (tHb) via near-infrared spectroscopy and lower leg blood flow (LBF) as popliteal flow velocity via Doppler ultrasound in the same leg.

Results

LBF increased by Δ9.73 ± 0.66 cm/s and peaked 4.4 min after NO administration and declined slowly but remained elevated (Δ3.63 ± 0.60 cm/s) at 10 min. In contrast, time to peak response was longer and smaller in magnitude in the tibia as tHb increased Δ2.08 ± 0.22 μM and peaked 5.3 min after NO administration and declined quickly but remained elevated (Δ0.87±0.22 μM) at 10 min (p = .01).

Conclusions

In young adults, the tibial vasculature demonstrates robust NO-mediated vasodilation, but tHb is delayed and diminishes faster compared to LBF, predominately reflective of skeletal muscle responses. Thus, NO-mediated vasodilation in bone may be characteristically different from other vascular beds.

目的：骨血流的调节至关重要，但人们对其了解甚少，尤其是对人类而言。本研究旨在确定一氧化氮（NO）作为其他组织血管张力的主要调节剂，是否也有助于调节骨骼的血流量：在年轻健康成人（n = 16，8F，8M）中，我们描述了一氧化氮介导的胫骨血管扩张对舌下含服硝酸甘油的反应，并将其与小腿进行对比。通过近红外光谱连续测量胫骨总血红蛋白（tHb）和小腿血流（LBF）（即同一腿部的腘绳肌血流速度），对仰卧者的血流反应进行了评估：施用 NO 后 4.4 分钟，小腿血流速度增加了 Δ9.73 ± 0.66 厘米/秒，达到峰值，随后缓慢下降，但在 10 分钟后仍保持升高（Δ3.63 ± 0.60 厘米/秒）。相比之下，胫骨的峰值反应时间更长，幅度更小，因为 tHb 增加了 Δ2.08 ± 0.22 μM，在施用 NO 后 5.3 分钟达到峰值，并迅速下降，但在 10 分钟时仍保持升高（Δ0.87±0.22 μM）（p = .01）：结论：在青壮年中，胫骨血管表现出强有力的 NO 介导的血管舒张，但与 LBF 相比，tHb 的延迟和减少速度更快，这主要反映了骨骼肌的反应。因此，NO介导的骨骼血管舒张可能与其他血管床有本质区别。

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引用次数: 0

Endothelial deficiency of insulin-like growth factor-1 receptor leads to blood–brain barrier disruption and accelerated endothelial senescence in mice, mimicking aspects of the brain aging phenotype 小鼠内皮细胞缺乏胰岛素样生长因子-1 受体会导致血脑屏障破坏和内皮细胞加速衰老，从而模拟大脑衰老表型的各个方面

IF 2.4 4区医学 Q3 HEMATOLOGY

Microcirculation

Pub Date : 2023-12-11 DOI: 10.1111/micc.12840

Rafal Gulej, Boglarka Csik, Janet Faakye, Stefano Tarantini, Santny Shanmugarama, Siva Sai Chandragiri, Peter Mukli, Shannon Conley, Anna Csiszar, Zoltan Ungvari, Andriy Yabluchanskiy, Ádám Nyúl-Tóth

Introduction

Age-related blood–brain barrier (BBB) disruption, cerebromicrovascular senescence, and microvascular rarefaction substantially contribute to the pathogenesis of vascular cognitive impairment (VCI) and Alzheimer's disease (AD). Previous studies established a causal link between age-related decline in circulating levels of insulin-like growth factor-1 (IGF-1), cerebromicrovascular dysfunction, and cognitive decline. The aim of our study was to determine the effect of IGF-1 signaling on senescence, BBB permeability, and vascular density in middle-age and old brains.

Methods

Accelerated endothelial senescence was assessed in senescence reporter mice (VE-Cadherin-Cre^ERT2/Igf1r^fl/fl × p16-3MR) using flow cytometry. To determine the functional consequences of impaired IGF-1 input to cerebromicrovascular endothelial cells, BBB integrity and capillary density were studied in mice with endothelium-specific knockout of IGF1R (VE-Cadherin-Cre^ERT2/Igf1r^fl/fl) using intravital two-photon microscopy.

Results

In VE-Cadherin-Cre^ERT2/Igf1r^fl/fl mice: (1) there was an increased presence of senescent endothelial cells; (2) cumulative permeability of the microvessels to fluorescent tracers of different molecular weights (0.3–40 kDa) is significantly increased, as compared to that of control mice, whereas decline in cortical capillary density does not reach statistical significance.

Conclusions

These findings support the notion that IGF-1 signaling plays a crucial role in preserving a youthful cerebromicrovascular endothelial phenotype and maintaining the integrity of the BBB.

与年龄相关的血脑屏障（BBB）破坏、脑微血管衰老和微血管稀疏是血管性认知障碍（VCI）和阿尔茨海默病（AD）的主要发病机制。以往的研究证实，与年龄相关的胰岛素样生长因子-1（IGF-1）循环水平下降、脑微血管功能障碍和认知能力下降之间存在因果关系。我们的研究旨在确定 IGF-1 信号对中老年大脑衰老、BBB 通透性和血管密度的影响。

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引用次数: 0

Abstracts from the 48th Annual Meeting of Japanese Society for Microcirculation 第 48 届日本微循环学会年会论文摘要

IF 2.4 4区医学 Q3 HEMATOLOGY

Microcirculation

Pub Date : 2023-12-08 DOI: 10.1111/micc.12836

引用次数: 0

Flow-dependent regulation of rat mesenteric lymphatic vessel contractile response requires activation of endothelial TRPV4 channels 大鼠肠系膜淋巴管收缩反应的血流依赖性调节需要内皮TRPV4通道的激活。

IF 2.4 4区医学 Q3 HEMATOLOGY

Microcirculation

Pub Date : 2023-12-04 DOI: 10.1111/micc.12839

Jacques DuToit, Peter Brothers, Matthew Stephens, Keith Keane, Flavia Neto de Jesus, Simon Roizes, Pierre-Yves von der Weid

Objectives

The objective of our study is to evaluate the involvement of the transient receptor potential vanilloid 4 (TRPV4) in the alteration of lymphatic pumping in response to flow and determine the signaling pathways involved.

Methods

We used immunofluorescence imaging and western blotting to assess TRPV4 expression in rat mesenteric lymphatic vessels. We examined inhibition of TRPV4 with HC067047, nitric oxide synthase (NOS) with L-NNA and cyclooxygenases (COXs) with indomethacin on the contractile response of pressurized lymphatic vessels to flow changes induced by a stepwise increase in pressure gradients, and the functionality of endothelial TRPV4 channels by measuring the intracellular Ca²⁺ response of primary lymphatic endothelial cell cultures to the selective agonist GSK1016790A.

Results

TRPV4 protein was expressed in both the endothelial and the smooth muscle layer of rat mesenteric lymphatics with high endothelial expression around the valve sites. When maintained under constant transmural pressure, most lymphatic vessels displayed a decrease in contraction frequency under conditions of flow and this effect was ablated through inhibition of NOS, COX or TRPV4.

Conclusions

Our findings demonstrate a critical role for TRPV4 in the decrease in contraction frequency induced in lymphatic vessels by increases in flow rate via the production and action of nitric oxide and dilatory prostanoids.

目的:我们研究的目的是评估瞬时受体电位香草样蛋白4 (TRPV4)在淋巴泵送对血流反应的改变中的作用，并确定所涉及的信号通路。方法:采用免疫荧光成像和免疫印迹法检测大鼠肠系膜淋巴管中TRPV4的表达。我们研究了HC067047对TRPV4的抑制作用，L-NNA对一氧化氮合酶(NOS)的抑制作用，吲哚美辛对环氧合酶(cox)对加压淋巴血管对压力梯度逐步增加引起的血流变化的收缩反应的抑制作用，以及通过测量原代淋巴内皮细胞培养物对选择性激动剂GSK1016790A的细胞内Ca2+反应来检测内皮细胞TRPV4通道的功能。结果:TRPV4蛋白在大鼠肠系膜淋巴管内皮层和平滑肌层均有表达，并在瓣膜周围高表达。当维持在恒定的跨壁压力下时，大多数淋巴管在流动条件下表现出收缩频率的降低，这种影响通过抑制NOS、COX或TRPV4来消除。结论:我们的研究结果表明，TRPV4在通过一氧化氮和扩张性前列腺素的产生和作用引起的流速增加而引起的淋巴管收缩频率降低中起关键作用。

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引用次数: 0

Emerging role of YAP/TAZ in vascular mechanotransduction and disease YAP/TAZ在血管机械转导和疾病中的新作用。

IF 2.4 4区医学 Q3 HEMATOLOGY

Microcirculation

Pub Date : 2023-11-27 DOI: 10.1111/micc.12838

Olivia Ritsvall, Sebastian Albinsson

Cells have an incredible ability to physically interact with neighboring cells and their environment. They can detect and respond to mechanical forces by converting mechanical stimuli into biochemical signals in a process known as mechanotransduction. This is a key process for the adaption of vascular smooth muscle and endothelial cells to altered flow and pressure conditions. Mechanical stimuli, referring to a physical force exerted on cells, are primarily sensed by transmembrane proteins and the actin cytoskeleton, which initiate a cascade of intracellular events, including the activation of signaling pathways, ion channels, and transcriptional regulators. Recent work has highlighted an important role of the transcriptional coactivators YAP/TAZ for mechanotransduction in vascular cells. Interestingly, the activity of YAP/TAZ decreases with age, providing a potential mechanism for the detrimental effects of aging in the vascular wall. In this review, we summarize the current knowledge on the functional role of YAP and TAZ in vascular endothelial and smooth muscle cells for mechanotransduction in homeostasis and disease. In particular, the review is focused on in vivo observations from conditional knockout (KO) models of YAP/TAZ and the potential implications these studies may have for our understanding of vascular disease development.

细胞具有与邻近细胞及其环境相互作用的惊人能力。它们可以通过将机械刺激转化为生化信号来检测机械力并做出反应，这一过程被称为机械转导。这是血管平滑肌和内皮细胞适应血流和压力变化的关键过程。机械刺激是指施加在细胞上的物理力，主要由跨膜蛋白和肌动蛋白细胞骨架感知，它们启动一系列细胞内事件，包括信号通路、离子通道和转录调节因子的激活。最近的研究强调了转录共激活因子YAP/TAZ在血管细胞机械转导中的重要作用。有趣的是，YAP/TAZ的活性随着年龄的增长而下降，这为衰老对血管壁的有害影响提供了一种潜在的机制。本文综述了YAP和TAZ在血管内皮细胞和平滑肌细胞内稳态和疾病中机械转导的功能作用。该综述特别关注YAP/TAZ的条件敲除(KO)模型的体内观察，以及这些研究可能对我们理解血管疾病发展的潜在影响。

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引用次数: 0

Advanced glycated end-products inhibit dilation through constitutive endothelial RAGE and Nox1/4 in rat isolated skeletal muscle arteries 晚期糖基化终产物通过构成性内皮RAGE和Nox1/4抑制大鼠离体骨骼肌动脉的扩张。

IF 2.4 4区医学 Q3 HEMATOLOGY

Microcirculation

Pub Date : 2023-11-20 DOI: 10.1111/micc.12837

Nadim Naser, Chenchel K. Lonj, Matthew Rikard-Bell, Shaun L. Sandow, Timothy V. Murphy

Objective

This study investigated the actions of advanced glycated end-products (AGE), their receptors (RAGE), and NAD(P)H oxidase (Nox) subtypes 1, 2, and 4 on mechanisms of endothelium-dependent dilation of the rat cremaster muscle artery (CMA).

Methods

Immunofluorescence studies were used to examine expression of RAGE in rat arteries. ROS accumulation was measured using luminescence and fluorescence assays. Functional studies were performed using pressure myography.

Results

High levels of RAGE expression were shown in the endothelial cells of the CMA, compared with low endothelial expression in middle cerebral and mesenteric arteries and the aorta. Exogenous AGE (in vitro glycated bovine serum albumin) stimulated H2O2 accumulation in CMA, which was prevented by the RAGE antagonist FPS-ZM1, the NAD(P)H oxidase (Nox) inhibitor apocynin and inhibited by the Nox1/4 inhibitor setanaxib, but not the Nox2 inhibitor GSK2795039. In functional studies, AGE inhibited vasodilation of CMA stimulated by acetylcholine, sodium nitroprusside, and the BKCa activator NS1619, but not adenosine-induced dilation. FPS-ZM1, apocynin, and setanaxib prevented the inhibitory effects of AGE on responses to acetylcholine and NS-1619.

Conclusion

These observations suggest RAGE are constitutively expressed in the endothelium of the rat CMA and may be activated by AGE to stimulate Nox1/4 and ROS formation with resulting inhibition of NO and BKCa-mediated endothelium-dependent dilation.

目的:研究晚期糖基化终产物(AGE)及其受体(RAGE)和NAD(P)H氧化酶(Nox)亚型1、2和4对大鼠肌动脉(CMA)内皮依赖性扩张的作用机制。方法:采用免疫荧光法检测RAGE在大鼠动脉组织中的表达。用发光和荧光法测定ROS积累。使用压力肌图进行功能研究。结果:RAGE在CMA内皮细胞中呈高表达，而在大脑中动脉、肠系膜动脉和主动脉中呈低表达。外源性AGE(体外糖化牛血清白蛋白)刺激CMA中H2O2的积累，RAGE拮抗剂FPS-ZM1和NAD(P)H氧化酶(Nox)抑制剂apocynin可以阻止H2O2的积累，Nox1/4抑制剂setanaxb可以抑制H2O2的积累，但Nox2抑制剂GSK2795039不能抑制H2O2的积累。在功能研究中，AGE抑制乙酰胆碱、硝普钠和BKCa激活剂NS1619刺激的CMA血管舒张，但不抑制腺苷诱导的舒张。FPS-ZM1、罗布麻素和西他那西可阻止AGE对乙酰胆碱和NS-1619的抑制作用。结论:RAGE在大鼠CMA的内皮中组成性表达，并可能被AGE激活，刺激Nox1/4和ROS的形成，从而抑制NO和bkca介导的内皮依赖性扩张。

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引用次数: 0

Vascular persistence following precision micropuncture 精密微穿刺后的血管持久性。

IF 2.4 4区医学 Q3 HEMATOLOGY

Microcirculation

Pub Date : 2023-11-10 DOI: 10.1111/micc.12835

Summer N. Horchler, Patrick C. Hancock, Mingjie Sun, Alexander T. Liu, Sameer Massand, Jessica C. El-Mallah, Dana Goldenberg, Olivia Waldron, Mary E. Landmesser, Shailaja Agrawal, Srinivas V. Koduru, Dino J. Ravnic

Objective

The success of engineered tissues continues to be limited by time to vascularization and perfusion. Recently, we described a simple microsurgical approach, termed micropuncture (MP), which could be used to rapidly vascularize an adjacently placed scaffold from the recipient macrovasculature. Here we studied the long-term persistence of the MP-induced microvasculature.

Methods

Segmental 60 μm diameter MPs were created in the recipient rat femoral artery and vein followed by coverage with a simple Type 1 collagen scaffold. The recipient vasculature and scaffold were then wrapped en bloc with a silicone sheet to isolate intrinsic vascularization. Scaffolds were harvested at 28 days post-implantation for detailed analysis, including using a novel artificial intelligence (AI) approach.

Results

MP scaffolds demonstrated a sustained increase of vascular density compared to internal non-MP control scaffolds (p < 0.05) secondary to increases in both vessel diameters (p < 0.05) and branch counts (p < 0.05). MP scaffolds also demonstrated statistically significant increases in red blood cell (RBC) perfused lumens.

Conclusions

This study further highlights that the intrinsic MP-induced vasculature continues to persist long-term. Its combination of rapid and stable angiogenesis represents a novel surgical platform for engineered scaffold and graft perfusion.

目的：工程组织的成功仍然受到血管化和灌注时间的限制。最近，我们描述了一种简单的显微外科方法，称为微穿刺（MP），可用于从受体大血管系统快速为相邻放置的支架提供血管。在这里，我们研究了MP诱导的微血管的长期持续性。方法：Segmental 60 在受体大鼠股动脉和静脉中产生直径为μm的MP，然后用简单的1型胶原支架覆盖。然后用硅胶片整体包裹受体血管系统和支架，以分离内在血管形成。脚手架于28日收割植入后几天进行详细分析，包括使用新型人工智能（AI）方法。结果：与内部非MP对照支架相比，MP支架显示出血管密度的持续增加（p 结论：这项研究进一步强调了MP诱导的固有血管系统继续长期存在。它结合了快速和稳定的血管生成，为工程支架和移植物灌注提供了一种新的手术平台。

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引用次数: 0

Vascular polycystin proteins in health and disease 血管性多囊蛋白在健康和疾病中的作用。

IF 2.4 4区医学 Q3 HEMATOLOGY

Microcirculation

Pub Date : 2023-10-12 DOI: 10.1111/micc.12834

Ulrich C. Mbiakop, Jonathan H. Jaggar

PKD1 (polycystin 1) and PKD2 (polycystin 2) are expressed in a variety of different cell types, including arterial smooth muscle and endothelial cells. PKD1 is a transmembrane domain protein with a large extracellular N-terminus that is proposed to act as a mechanosensor and receptor. PKD2 is a member of the transient receptor potential (TRP) channel superfamily which is also termed TRPP1. Mutations in the genes which encode PKD1 and PKD2 lead to autosomal dominant polycystic kidney disease (ADPKD). ADPKD is one of the most prevalent monogenic disorders in humans and is associated with extrarenal and vascular complications, including hypertension. Recent studies have uncovered mechanisms of activation and physiological functions of PKD1 and PKD2 in arterial smooth muscle and endothelial cells. It has also been found that PKD function is altered in the vasculature during ADPKD and hypertension. We will summarize this work and discuss future possibilities for this area of research.

PKD1（多囊蛋白1）和PKD2（多囊蛋白2）在多种不同的细胞类型中表达，包括动脉平滑肌和内皮细胞。PKD1是一种跨膜结构域蛋白，具有大的细胞外N末端，被认为是一种机械传感器和受体。PKD2是瞬时受体电位（TRP）通道超家族的成员，也称为TRPP1。编码PKD1和PKD2的基因突变导致常染色体多囊肾病（ADPKD）。ADPKD是人类最常见的单基因疾病之一，与肾外和血管并发症有关，包括高血压。最近的研究揭示了PKD1和PKD2在动脉平滑肌和内皮细胞中的激活机制和生理功能。还发现，在ADPKD和高血压期间，血管系统中的PKD功能发生改变。我们将总结这项工作，并讨论这一研究领域未来的可能性。

引用次数: 0