Arterial myogenic response and aging

Cui, Yingqiu; Gollasch, Maik; Kaßmann, Mario

doi:10.1016/j.arr.2022.101813

Cited by 4 publications

(2 citation statements)

References 174 publications

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“…Interestingly, only the mesenteric artery segments isolated from aged LPP-KO mice exhibited an impaired myogenic response. While there is some evidence that advanced age leads to an attenuated myogenic responsive in small arteries and arterioles of the mesentery [ 31 ], many studies demonstrate this effect of aging also in other vascular beds (as summarized in [ 32 ]). Accordingly, our data suggest that LPP as an important regulator of actin dynamics helps properly organize the actin cytoskeleton and maintain the phenotype of the medial VSMCs, thereby sustaining the elastic properties of the blood vessel wall.…”

Section: Discussionmentioning

confidence: 99%

Characterisation of Lipoma-Preferred Partner as a Novel Mechanotransducer in Vascular Smooth Muscle Cells

Sporkova,

Nahar,

Cao

et al. 2023

Cells

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In arteries and arterioles, a chronic increase in blood pressure raises wall tension. This continuous biomechanical strain causes a change in gene expression in vascular smooth muscle cells (VSMCs) that may lead to pathological changes. Here we have characterised the functional properties of lipoma-preferred partner (LPP), a Lin11–Isl1–Mec3 (LIM)-domain protein, which is most closely related to the mechanotransducer zyxin but selectively expressed by smooth muscle cells, including VSMCs in adult mice. VSMCs isolated from the aorta of LPP knockout (LPP-KO) mice displayed a higher rate of proliferation than their wildtype (WT) counterparts, and when cultured as three-dimensional spheroids, they revealed a higher expression of the proliferation marker Ki 67 and showed greater invasion into a collagen gel. Accordingly, the gelatinase activity was increased in LPP-KO but not WT spheroids. The LPP-KO spheroids adhering to the collagen gel responded with decreased contraction to potassium chloride. The relaxation response to caffeine and norepinephrine was also smaller in the LPP-KO spheroids than in their WT counterparts. The overexpression of zyxin in LPP-KO VSMCs resulted in a reversal to a more quiescent differentiated phenotype. In native VSMCs, i.e., in isolated perfused segments of the mesenteric artery (MA), the contractile responses of LPP-KO segments to potassium chloride, phenylephrine or endothelin-1 did not vary from those in isolated perfused WT segments. In contrast, the myogenic response of LPP-KO MA segments was significantly attenuated while zyxin-deficient MA segments displayed a normal myogenic response. We propose that LPP, which we found to be expressed solely in the medial layer of different arteries from adult mice, may play an important role in controlling the quiescent contractile phenotype of VSMCs.

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Section: Discussionmentioning

confidence: 99%

Characterisation of Lipoma-Preferred Partner as a Novel Mechanotransducer in Vascular Smooth Muscle Cells

Sporkova,

Nahar,

Cao

et al. 2023

Cells

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“…Small-artery and resistance-vessel regulation is the key element regulating blood pressure and blood flow. 10 , 11 Systemic vascular resistance in hypertension “is not everything; it is the only thing”. Vasoconstriction is mediated by increased intracellular Ca 2+ concentration in vascular smooth muscle cells (VSMCs).…”

Section: Expected Outcomesmentioning

confidence: 99%

Protocol for assessing myogenic tone and perfusion pressure in isolated mouse kidneys

Chu,

Kassmann,

Anistan

et al. 2024

STAR Protocols

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Oxidative DNA damage promotes vascular ageing associated with changes in extracellular matrix-regulating proteins

Foote,

Rienks,

Schmidt

et al. 2024

Cardiovascular Research

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Aims Vascular aging is characterized by vessel stiffening, with increased deposition of extracellular matrix (ECM) proteins including collagens. Oxidative DNA damage occurs in vascular aging, but how it regulates ECM proteins and vascular stiffening is unknown. We sought to determine the relationship between oxidative DNA damage and ECM regulatory proteins in vascular aging. Methods and Results We examined oxidative DNA damage, the major base excision repair (BER) enzyme 8-Oxoguanine DNA Glycosylase (Ogg1) and its regulators, multiple physiological markers of aging, and ECM proteomics in mice from 22-72w. Vascular aging was associated with increased oxidative DNA damage, and decreased expression of Ogg1, its active acetylated form, its acetylation regulatory proteins P300 and CBP, and the transcription factor Foxo3a. Vascular stiffness was examined in vivo in control, Ogg1-/-, or mice with vascular smooth muscle cell-specific expression of Ogg1+ (Ogg1) or an inactive mutation (Ogg1KR). Ogg1-/- and Ogg1KR mice showed reduced arterial compliance and distensibility, and increased stiffness and pulse pressure, whereas Ogg1 expression normalised all parameters to 72w. ECM proteomics identified major changes in collagens with aging, and downregulation of the ECM regulatory proteins Protein 6-lysyl oxidase (LOX) and WNT1-inducible-signaling pathway protein 2 (WISP2). Ogg1 overexpression upregulated LOX and WISP2 both in vitro and in vivo, and downregulated Transforming growth factor β1 (TGFb1) and Collagen 4α1 in vivo compared with Ogg1KR. Foxo3a activation induced Lox, while Wnt3 induction of Wisp2 also upregulated LOX and Foxo3a, and downregulated TGFβ1 and fibronectin 1. In humans, 8-oxo-G increased with vascular stiffness, while active OGG1 reduced with both age and stiffness. Conclusions Vascular aging is associated with oxidative DNA damage, downregulation of major BER proteins, and changes in multiple ECM structural and regulatory proteins. Ogg1 protects against vascular aging, associated with changes in ECM regulatory proteins including LOX and WISP2.

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Arterial myogenic response and aging

Cited by 4 publications

References 174 publications

Characterisation of Lipoma-Preferred Partner as a Novel Mechanotransducer in Vascular Smooth Muscle Cells

Characterisation of Lipoma-Preferred Partner as a Novel Mechanotransducer in Vascular Smooth Muscle Cells

Protocol for assessing myogenic tone and perfusion pressure in isolated mouse kidneys

Oxidative DNA damage promotes vascular ageing associated with changes in extracellular matrix-regulating proteins

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