Epigenetic regulators of the revascularization response to chronic arterial occlusion
| Autor: | Joshua L. Heuslein, Catherine M. Gorick, Richard J. Price |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Physiology medicine.medical_treatment Ischemia Reviews Collateral Circulation Neovascularization Physiologic Context (language use) Hindlimb 030204 cardiovascular system & hematology Artery morphogenesis Bioinformatics Revascularization Epigenesis Genetic Mice Peripheral Arterial Disease 03 medical and health sciences 0302 clinical medicine Physiology (medical) medicine Animals Humans Regeneration Epigenetics Muscle Skeletal business.industry medicine.disease Arterial occlusion Rats Disease Models Animal 030104 developmental biology Regional Blood Flow Chronic Disease Arteriogenesis Cardiology and Cardiovascular Medicine business |
| Zdroj: | Cardiovascular Research. 115:701-712 |
| ISSN: | 1755-3245 0008-6363 |
| DOI: | 10.1093/cvr/cvz001 |
| Popis: | Peripheral arterial disease (PAD) is the leading cause of lower limb amputation and estimated to affect over 202 million people worldwide. PAD is caused by atherosclerotic lesions that occlude large arteries in the lower limbs, leading to insufficient blood perfusion of distal tissues. Given the severity of this clinical problem, there has been long-standing interest in both understanding how chronic arterial occlusions affect muscle tissue and vasculature and identifying therapeutic approaches capable of restoring tissue composition and vascular function to a healthy state. To date, the most widely utilized animal model for performing such studies has been the ischaemic mouse hindlimb. Despite not being a model of PAD per se, the ischaemic hindlimb model does recapitulate several key aspects of PAD. Further, it has served as a valuable platform upon which we have built much of our understanding of how chronic arterial occlusions affect muscle tissue composition, muscle regeneration and angiogenesis, and collateral arteriogenesis. Recently, there has been a global surge in research aimed at understanding how gene expression is regulated by epigenetic factors (i.e. non-coding RNAs, histone post-translational modifications, and DNA methylation). Thus, perhaps not unexpectedly, many recent studies have identified essential roles for epigenetic factors in regulating key responses to chronic arterial occlusion(s). In this review, we summarize the mechanisms of action of these epigenetic regulators and highlight several recent studies investigating the role of said regulators in the context of hindlimb ischaemia. In addition, we focus on how these recent advances in our understanding of the role of epigenetics in regulating responses to chronic arterial occlusion(s) can inform future therapeutic applications to promote revascularization and perfusion recovery in the setting of PAD. |
| Databáze: | OpenAIRE |
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