Exercise and Ischemia-Activated Pathways in Limb Muscle Angiogenesis and Vascular Regeneration

Narkar, Vihang A.

doi:10.14797/mdcvj.1304

Cited by 4 publications

(1 citation statement)

References 95 publications

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“…Notably, angiogenesis after the completion of individual development primarily occurs in conjunction with a chronic inflammatory response [267]. Chronic inflammation and hypoxia, which are the principal physiological stimuli that induce angiogenesis, clearly coincide [268,269]. Therefore, inflammation and angiogenesis, including tumor angiogenesis, are two interdependent processes that may enhance each other [266,269].…”

Section: Interdependence Of Inflammation and Angiogenesismentioning

confidence: 99%

CX3CL1 (Fractalkine)-CX3CR1 Axis in Inflammation-Induced Angiogenesis and Tumorigenesis

Szukiewicz

2024

Preprint

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The chemotactic cytokine fractalkine (FKN, chemokine CX3CL1) has unique properties resulting from the combination of chemoattractants and adhesion molecules. The soluble form (sFKN) has chemotactic properties and potently attracts T cells and monocytes. The membrane-bound form (mFKN) facilitates diapedesis and is responsible for cell-to-cell adhesion, especially by promoting the strong adhesion of leukocytes (monocytes) to activated endothelial cells with the subsequent formation of an extracellular matrix and angiogenesis. FKN signaling occurs via CX3CR1, which is the only known member of the CX3C chemokine receptor subfamily. Signaling within the FKN-CX3CR1 axis plays an important role in many processes related to inflammation and the immune response, which often occur simultaneously and overlap. FKN is strongly upregulated by hypoxia and/or inflammation-induced inflammatory cytokine secretion, and it may act locally as a key angiogenic factor in the highly hypoxic tumor microenvironment. The importance of the FKN/CX3CR1 signaling pathway in tumorigenesis and cancer metastasis results from its influence on cell adhesion, apoptosis and cell migration. This review presents the role of the FKN signaling pathway in the context of angiogenesis in inflammation and cancer. The mechanisms determining the pro- or anti-tumor effects are presented, which are the cause of the seemingly contradictory results that create confusion regarding the therapeutic goals.

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Section: Interdependence Of Inflammation and Angiogenesismentioning

confidence: 99%

CX3CL1 (Fractalkine)-CX3CR1 Axis in Inflammation-Induced Angiogenesis and Tumorigenesis

Szukiewicz

2024

Preprint

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A 6-Minute Limb Function Assessment for Therapeutic Testing in Experimental Peripheral Artery Disease Models

Palzkill,

Tan,

Moparthy

et al. 2024

JACC: Basic to Translational Science

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A 6-minute Limb Function Assessment for Therapeutic Testing in Experimental Peripheral Artery Disease Models

Palzkill,

Tan,

Tice

et al. 2024

Preprint

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Objective: The translation of promising therapies from pre-clinical models of hindlimb ischemia (HLI) to patients with peripheral artery disease (PAD) has been inadequate. While this failure is multifactorial, primary outcome measures in preclinical HLI models and clinical trials involving patients with PAD are not aligned well. For example, laser Doppler perfusion recovery measured under resting conditions is the most used outcome in HLI studies, whereas clinical trials involving patients with PAD primarily assess walking performance. Here, we develop a 6-min limb function test for preclinical models that assesses muscular performance and hemodynamics congruently. Approach and Results: We developed an in situ 6-min limb function test that involves repeated isotonic (shortening) contractions performed against a submaximal load. Continuous measurement of muscle blood flow was performed using laser Doppler flowmetry. Quantification of muscle power, work, and perfusion are obtained across the test. We performed HLI on several mouse strains: C57BL6J, BALBc/J, and MCK-PGC1a (muscle-specific overexpression of PGC1a). Additional experiments were performed using an exercise intervention (voluntary wheel running) following HLI. The 6-min limb function test was successful at detecting differences in limb function of C57BL6/J and BALBc/J mice subjected to HLI with effect sizes superior to laser Doppler. C57BL6/J mice randomized to exercise therapy following HLI had smaller decline in muscle power, greater hyperemia, and performed more work compared to non-exercise controls with HLI. Mice with muscle-specific overexpression of PGC1a had no differences in perfusion recovery in resting conditions, but exhibited greater capillary density, increased muscle mass and absolute force levels, and performed more work across the 6-min limb function test compared to their wildtype littermates. Conclusion: These results demonstrate the efficacy of the 6-min limb function test to detect differences in the response to HLI where traditional perfusion recovery, capillary density, and muscle strength measures were unable to detect therapeutic differences.

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Exercise and Ischemia-Activated Pathways in Limb Muscle Angiogenesis and Vascular Regeneration

Cited by 4 publications

References 95 publications

CX3CL1 (Fractalkine)-CX3CR1 Axis in Inflammation-Induced Angiogenesis and Tumorigenesis

CX3CL1 (Fractalkine)-CX3CR1 Axis in Inflammation-Induced Angiogenesis and Tumorigenesis

A 6-Minute Limb Function Assessment for Therapeutic Testing in Experimental Peripheral Artery Disease Models

A 6-minute Limb Function Assessment for Therapeutic Testing in Experimental Peripheral Artery Disease Models

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