Regulation of Proteolysis in Vascular Remodeling

Mandel, Erin R.; Uchida, Cassandra; Haas, Tara L.

doi:10.1007/978-1-4614-9099-9_16

Cited by 2 publications

(2 citation statements)

References 191 publications

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“…For example, TIMP1 is postulated to exert pro-proliferative and pro-survival cues in cancer cells (Stetler-Stevenson 2008). However, we have not been able to detect this effect in cultured endothelial cells (Mandel et al 2014), thus the potential relevance of these functions to endothelial cell behaviour remains poorly established. We found that exposure of endothelial cells to elevated shear stress induces the increased production of TIMP1, indicating that TIMP1 may play a protective anti-proteolytic role that assists in maintaining capillary integrity in the face of elevated hemodynamic stress (Milkiewicz et al 2008;Uchida and Haas 2014).…”

Section: Pro-angiogenic Factorsmentioning

confidence: 74%

Regulation of skeletal muscle capillary growth in exercise and disease

Haas

Nwadozi

2015

Appl. Physiol. Nutr. Metab.

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Capillaries, which are the smallest and most abundant type of blood vessel, form the primary site of gas, nutrient, and waste transfer between the vascular and tissue compartments. Skeletal muscle exhibits the capacity to generate new capillaries (angiogenesis) as an adaptation to exercise training, thus ensuring that the heightened metabolic demand of the active muscle is matched by an improved capacity for distribution of gases, nutrients, and waste products. This review summarizes the current understanding of the regulation of skeletal muscle capillary growth. The multi-step process of angiogenesis is coordinated through the integration of a diverse array of signals associated with hypoxic, metabolic, hemodynamic, and mechanical stresses within the active muscle. The contributions of metabolic and mechanical factors to the modulation of key pro- and anti-angiogenic molecules are discussed within the context of responses to a single aerobic exercise bout and short-term and long-term training. Finally, the paradoxical lack of angiogenesis in peripheral artery disease and diabetes and the implications for disease progression and muscle health are discussed. Future studies that emphasize an integrated analysis of the mechanisms that control skeletal muscle capillary growth will enable development of targeted exercise programs that effectively promote angiogenesis in healthy individuals and in patient populations.

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Section: Pro-angiogenic Factorsmentioning

confidence: 74%

Regulation of skeletal muscle capillary growth in exercise and disease

Haas

Nwadozi

2015

Appl. Physiol. Nutr. Metab.

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“…It has been reported that TIMP1 exerts MMP‐independent functions that influence cell survival and proliferation (reviewed in Ries, ). However, our laboratory found that recombinant TIMP1 did not impact survival of cultured endothelial cells (Mandel et al, ). This, together with a lack of detectable apoptosis in Timp1 −/− muscle in the current study, suggests that TIMP1 deletion does not directly impact endothelial cell apoptotic signaling.…”

Section: Discussionmentioning

confidence: 99%

Tissue Inhibitor of Metalloproteinase 1 Influences Vascular Adaptations to Chronic Alterations in Blood Flow

Mandel

Uchida

Nwadozi

et al. 2016

Journal Cellular Physiology

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Remodeling of the skeletal muscle microvasculature involves the coordinated actions of matrix metalloproteinases (MMPs) and their endogenous inhibitors, tissue inhibitor of metalloproteinases (TIMPs). We hypothesized that the loss of TIMP1 would enhance both ischemia and flow-induced vascular remodeling by increasing MMP activity. TIMP1 deficient (Timp1 ) and wild-type (WT) C57BL/6 mice underwent unilateral femoral artery (FA) ligation or were treated with prazosin, an alpha-1 adrenergic receptor antagonist, in order to investigate vascular remodeling to altered flow. Under basal conditions, Timp1 mice had reduced microvascular content as compared to WT mice. Furthermore, vascular remodeling was impaired in Timp1 mice. Timp1 mice displayed reduced blood flow recovery in response to FA ligation and no arteriogenic response to prazosin treatment. Timp1 mice failed to undergo angiogenesis in response to ischemia or prazosin, despite maintaining the capacity to increase VEGF-A and eNOS mRNA. Vascular permeability was increased in muscles of Timp1 mice in response to both prazosin treatment and FA ligation, but this was not accompanied by greater MMP activity. This study highlights a previously undescribed integral role for TIMP1 in both vascular network maturation and adaptations to ischemia or alterations in flow. J. Cell. Physiol. 232: 831-841, 2017. © 2016 Wiley Periodicals, Inc.

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Regulation of Proteolysis in Vascular Remodeling

Cited by 2 publications

References 191 publications

Regulation of skeletal muscle capillary growth in exercise and disease

Regulation of skeletal muscle capillary growth in exercise and disease

Tissue Inhibitor of Metalloproteinase 1 Influences Vascular Adaptations to Chronic Alterations in Blood Flow

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