Extracellular matrix dynamics in vascular remodeling

Ma, Zihan; Mao, Chenfeng; Jia, Yiting; Fu, Yi; Kong, Wei

doi:10.1152/ajpcell.00147.2020

Cited by 79 publications

(66 citation statements)

References 238 publications

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“…Healthy maternal vascular adaptations to pregnancy play an essential role in normal fetal growth and development. To achieve this, several hemodynamic changes occur, such as increased cardiac output, increased heart rate, and increased blood volume, while there is a decrease in blood pressure in early- to mid-gestation due to a reduced systemic vascular resistance during pregnancy ( Wang et al, 2015 ; Donato et al, 2018 ; Ma et al, 2020 ). Though the mechanisms of this reduced peripheral resistance are not completely understood, multiple studies have shown that during pregnancy the bioavailability of nitric oxide (NO), a potent endothelium-derived vasodilator, is increased ( Dorup et al, 1999 ; Valdes et al, 2009 ; Boeldt and Bird, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Altered Vascular Adaptations to Pregnancy in a Rat Model of Advanced Maternal Age

et al. 2021

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Advanced maternal age (≥35 years old) increases the risk of pregnancy complications such as preeclampsia and fetal growth restriction. We previously demonstrated vascular dysfunction and abnormal pregnancy outcomes in a rat model of advanced maternal age. However, vascular adaptations to pregnancy in aging were not studied. We hypothesize that advanced maternal age is associated with a more vasoconstrictive phenotype due to reduced nitric oxide (NO) and increased activity of matrix metalloproteinases (MMPs), contributing to impaired vascular adaptations to pregnancy. A rat model of advanced maternal age was used: young (4 months) and aged (9.5 months; ∼35 years in humans) non-pregnant and pregnant rats. On gestational day 20 (term = 22 days; non-pregnant rats were aged-matched), blood pressure and heart rate were measured (tail cuff plethysmography) and vascular function was assessed in mesenteric arteries (wire myography). Endothelium-dependent relaxation to methylcholine (MCh) was assessed in the presence/absence of nitric oxide synthase inhibitor (L-NAME), or inhibitors of endothelium-dependent hyperpolarization (EDH; apamin and TRAM-34). Vasoconstriction responses to big endothelin-1 (bigET-1), in the presence/absence of MMPs-inhibitor (GM6001) or endothelin converting enzyme (ECE-1) inhibitor (CGS35066), in addition, ET-1 responsiveness, were measured. Blood pressure was elevated only in aged non-pregnant rats (p < 0.001) compared to all other groups. MCh responses were not different, however, L-NAME decreased maximum vasodilation in young (p < 0.01) and aged pregnant rats (p < 0.001), and decreased MCh sensitivity in young non-pregnant rats (p < 0.01), without effects in aged non-pregnant rats. EDH contribution to relaxation was similar in young non-pregnant, and aged non-pregnant and pregnant rats, while EDH-mediated relaxation was absent in young pregnant rats (p < 0.001). BigET-1 responses were enhanced in aged non-pregnant (p < 0.01) and pregnant rats (p < 0.05). No significant changes in bigET-1 conversion occurred in the presence of MMP-inhibitor, whereas ECE-1 inhibition reduced bigET-1 constriction in aged rats (p < 0.01). No differences in ET-1 sensitivity were observed. In conclusion, contrary to our hypothesis, reduced blood pressure, and an increased EDH-dependent contribution to vasodilation suggest a compensatory mechanism that may reflect beneficial adaptations in these aged rats that were able to maintain pregnancy. These data increase our understanding of how the vascular adaptive pathways in pregnancy compensate for advanced maternal age.

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Section: Introductionmentioning

confidence: 99%

Altered Vascular Adaptations to Pregnancy in a Rat Model of Advanced Maternal Age

et al. 2021

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“…A release pro le analysis showed a sustained release of adipokines from ACF in vitro, and our uorescence tracing results indicated a gradual degradation process of ACF in vivo. Notably, the ECM serves as a natural reservoir of growth factors and releases them when exposed to the appropriate stimuli [45,46] . The mechanisms that regulate the release of ECM-bound growth factors are complex, including binding a nity, conformational changes, and degradation of the ECM [47,48] .…”

Section: Discussionmentioning

confidence: 99%

Adipose Collagen Fragment: an Injectable Sustained-release Collagen Scaffold of Adipokines for Preventing Skin Photoaging in Mice

Jin¹,

Zhang²,

Zhang³

et al. 2021

Preprint

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Objective: Ultraviolet A (UVA) radiation is the major contributor to skin photoaging, associated with increased collagen degradation and reactive oxygen species expression. Adipokines have been proven as promising therapeutic agents for skin photoaging. However, adipokine therapy is generally limited by the short in vivo release duration and biological instability. Therefore, developing a treatment that provides a sustained release of adipokines and enhanced therapeutic effects is desirable. Methods: Adipose collagen fragment (ACF) was prepared from lipoaspirate and characterized. The injectability, collagen components, and adipokine release pattern of ACF were identified in vitro. Then, we evaluated its therapeutic efficacy by injecting ACF and phosphate-buffered saline, as a control, into the dermis of photoaging nude mice and harvesting skin samples at weeks 1, 2, and 4 after treatment for assessment. The collagen synthesis and collagen degradation in ACF implants were evaluated by immune staining. Dermal thickness, fibroblast expression, collagen synthesis, reactive oxygen species level, antioxidase expression, capillary density, and apoptotic cell number were evaluated by histological assessment, immune staining, and polymerase chain reaction in the skin samples.Results: ACF is the concentrated adipose extracellular matrix collagen fragment without viable cells and can be injected through fine needles. ACF undergoes collagen degradation and promotes neocollagen synthesis in ACF implants. Meanwhile, ACF serves as a sustained-release system of adipokines and exhibits a significantly higher therapeutic effect on mouse skin photoaging compared to controls. ACF increases the dermal thickness, improves fibroblast expression and promotes collagen synthesis. ACF treatment of UVA-irradiated skin reduces reactive oxygen species expression, decreases the number of apoptotic cells, improves capillary density and promotes the expression of antioxidase superoxide dismutase-1, catalase and glutathione peroxidase-1 by sustainedly releasing adipokines.Conclusions: ACF is an adipokines-enriched, sustained-release extracellular matrix collagen scaffold that can prevent UVA-induced skin photoaging in mice. ACF may serve as a novel autologous skin filler for skin rejuvenation applications in the clinic.

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“…Together, these data reveal an involvement of ECM protein rearrangement in hyperleptinemia-induced vascular fibrosis. The ECM composition is an important determinant of arterial stiffness [ 118 ]. Disrupted balance between ECM synthesis and ECM degradation may trigger vascular remodeling resulting in structural, functional and mechanical changes in the vasculature.…”

Section: Leptin and Vascular Smooth Muscle Cellsmentioning

confidence: 99%

Leptin in Atherosclerosis: Focus on Macrophages, Endothelial and Smooth Muscle Cells

Raman

Khanal

2021

IJMS

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Increasing adipose tissue mass in obesity directly correlates with elevated circulating leptin levels. Leptin is an adipokine known to play a role in numerous biological processes including regulation of energy homeostasis, inflammation, vascular function and angiogenesis. While physiological concentrations of leptin may exhibit multiple beneficial effects, chronically elevated pathophysiological levels or hyperleptinemia, characteristic of obesity and diabetes, is a major risk factor for development of atherosclerosis. Hyperleptinemia results in a state of selective leptin resistance such that while beneficial metabolic effects of leptin are dampened, deleterious vascular effects of leptin are conserved attributing to vascular dysfunction. Leptin exerts potent proatherogenic effects on multiple vascular cell types including macrophages, endothelial cells and smooth muscle cells; these effects are mediated via an interaction of leptin with the long form of leptin receptor, abundantly expressed in atherosclerotic plaques. This review provides a summary of recent in vivo and in vitro studies that highlight a role of leptin in the pathogenesis of atherosclerotic complications associated with obesity and diabetes.

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Extracellular matrix dynamics in vascular remodeling

Cited by 79 publications

References 238 publications

Altered Vascular Adaptations to Pregnancy in a Rat Model of Advanced Maternal Age

Altered Vascular Adaptations to Pregnancy in a Rat Model of Advanced Maternal Age

Adipose Collagen Fragment: an Injectable Sustained-release Collagen Scaffold of Adipokines for Preventing Skin Photoaging in Mice

Leptin in Atherosclerosis: Focus on Macrophages, Endothelial and Smooth Muscle Cells

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