Endothelial mechanosensors: the gatekeepers of vascular homeostasis and adaptation under mechanical stress

Deng, Qiuping; Huo, Yingqing; Luo, Jincai

doi:10.1007/s11427-014-4705-3

Cited by 19 publications

(9 citation statements)

References 110 publications

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“…This study links whole-animal physiology, cardiac and pulmonary hemodynamics, microanatomy, and specific PAEC properties. PAECs are constantly under the influence of hemodynamic forces, including shear stress, the tangential friction force acting on the vessel wall due to blood flow (26); hydrostatic pressure, the perpendicular force acting on the vascular wall (27); and cyclic strain, the circumferential stretch of the vessel wall (28). Mechanosensors on these cells detect these forces and transduce them into biochemical signals that trigger vascular responses and ultimately pathologic hyperreactivity in PVD (29).…”

Section: Discussionmentioning

confidence: 99%

Ovine Models of Congenital Heart Disease and the Consequences of Hemodynamic Alterations for Pulmonary Artery Remodeling

Kameny¹,

Datar²,

Boehme³

et al. 2019

Am J Respir Cell Mol Biol

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The natural history of pulmonary vascular disease associated with congenital heart disease (CHD) depends on associated hemodynamics. Patients exposed to increased pulmonary blood flow (PBF) and pulmonary arterial pressure (PAP) develop pulmonary vascular disease more commonly than patients exposed to increased PBF alone. To investigate the effects of these differing mechanical forces on physiologic and molecular responses, we developed two models of CHD using fetal surgical techniques: 1) left pulmonary artery (LPA) ligation primarily resulting in increased PBF and 2) aortopulmonary shunt placement resulting in increased PBF and PAP. Hemodynamic, histologic, and molecular studies were performed on control, LPA, and shunt lambs as well as pulmonary artery endothelial cells (PAECs) derived from each. Physiologically, LPA, and to a greater extent shunt, lambs demonstrated an exaggerated increase in PAP in response to vasoconstricting stimuli compared with controls. These physiologic findings correlated with a pathologic increase in medial thickening in pulmonary arteries in shunt lambs but not in control or LPA lambs. Furthermore, in the setting of acutely increased afterload, the right ventricle of control and LPA but not shunt lambs demonstrates ventricular-vascular uncoupling and adverse ventricular-ventricular interactions. RNA sequencing revealed excellent separation between groups via both principal components analysis and unsupervised hierarchical clustering. In addition, we found hyperproliferation of PAECs from LPA lambs, and to a greater extent shunt lambs, with associated increased angiogenesis and decreased apoptosis in PAECs derived from shunt lambs. A further understanding of mechanical force-specific drivers of pulmonary artery pathology will enable development of precision therapeutics for pulmonary hypertension associated with CHD.

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Section: Discussionmentioning

confidence: 99%

Ovine Models of Congenital Heart Disease and the Consequences of Hemodynamic Alterations for Pulmonary Artery Remodeling

Kameny¹,

Datar²,

Boehme³

et al. 2019

Am J Respir Cell Mol Biol

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“…These transducers act as regulators of vascular homeostasis in tissues experiencing fluid flow (Deng et al, 2014). New vessel formation from the pre-existing vasculature is a feature of development and is more tightly regulated in adulthood.…”

Section: Mechanosensory Structural Components Of the Ah Outflow Symentioning

confidence: 99%

Aqueous outflow - A continuum from trabecular meshwork to episcleral veins

Carreon

Merwe

Fellman

et al. 2017

Progress in Retinal and Eye Research

240

196

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In glaucoma, lowered intraocular pressure (IOP) confers neuroprotection. Elevated IOP characterizes glaucoma and arises from impaired aqueous humor (AH) outflow. Increased resistance in the trabecular meshwork (TM), a filter-like structure essential to regulate AH outflow, may result in the impaired outflow. Flow through the 360° circumference of TM structures may be non-uniform, divided into high and low flow regions, termed as segmental. After flowing through the TM, AH enters Schlemm’s canal (SC), which expresses both blood and lymphatic markers; AH then passes into collector channel entrances (CCE) along the SC external well. From the CCE, AH enters a deep scleral plexus (DSP) of vessels that typically run parallel to SC. From the DSP, intrascleral collector vessels run radially to the scleral surface to connect with AH containing vessels called aqueous veins to discharge AH to blood-containing episcleral veins. However, the molecular mechanisms that maintain homeostatic properties of endothelial cells along the pathways are not well understood. How these molecular events change during aging and in glaucoma pathology remain unresolved. In this review, we propose mechanistic possibilities to explain the continuum of AH outflow control, which originates at the TM and extends through collector channels to the episcleral veins.

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“…The endothelium senses mechanical stress and mediates mechano-transduction through mechanosensors or mechanosensitive complexes 58 . Endothelial cells convert mechanical stress into intracellular biochemical signals, such as increased NO, H 2 S, and calcium concentration 59 - 61 .…”

Section: Endothelial Cell Functionsmentioning

confidence: 99%

Metformin in cardiovascular diabetology: a focused review of its impact on endothelial function

et al. 2021

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As a first-line treatment for diabetes, the insulin-sensitizing biguanide, metformin, regulates glucose levels and positively affects cardiovascular function in patients with diabetes and cardiovascular complications. Endothelial dysfunction (ED) represents the primary pathological change of multiple vascular diseases, because it causes decreased arterial plasticity, increased vascular resistance, reduced tissue perfusion and atherosclerosis. Caused by “biochemical injury”, ED is also an independent predictor of cardiovascular events. Accumulating evidence shows that metformin improves ED through liver kinase B1 (LKB1)/5'-adenosine monophosphat-activated protein kinase (AMPK) and AMPK-independent targets, including nuclear factor-kappa B (NF-κB), phosphatidylinositol 3 kinase-protein kinase B (PI3K-Akt), endothelial nitric oxide synthase (eNOS), sirtuin 1 (SIRT1), forkhead box O1 (FOXO1), krüppel-like factor 4 (KLF4) and krüppel-like factor 2 (KLF2). Evaluating the effects of metformin on endothelial cell functions would facilitate our understanding of the therapeutic potential of metformin in cardiovascular diabetology (including diabetes and its cardiovascular complications). This article reviews the physiological and pathological functions of endothelial cells and the intact endothelium, reviews the latest research of metformin in the treatment of diabetes and related cardiovascular complications, and focuses on the mechanism of action of metformin in regulating endothelial cell functions.

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Endothelial mechanosensors: the gatekeepers of vascular homeostasis and adaptation under mechanical stress

Cited by 19 publications

References 110 publications

Ovine Models of Congenital Heart Disease and the Consequences of Hemodynamic Alterations for Pulmonary Artery Remodeling

Ovine Models of Congenital Heart Disease and the Consequences of Hemodynamic Alterations for Pulmonary Artery Remodeling

Aqueous outflow - A continuum from trabecular meshwork to episcleral veins

Metformin in cardiovascular diabetology: a focused review of its impact on endothelial function

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