Narrative review of endothelial cell metabolism and aberrations in atherosclerosis and peripheral artery disease

Objective: Several decades of medical research have shown an intricate and definitive connection between dysfunctional endothelium and cardiovascular disorders, including atherosclerosis and peripheral artery disease (PAD). Initial investigations into endothelial cell (EC) physiology highlighted exc...

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Main Authors: Sean M. Carr, PhD, Ottis Scrivner, PhD, Katherine Elizabeth Hekman, MD, PhD
Format: Article
Language:English
Published: Elsevier 2025-01-01
Series:JVS - Vascular Science
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2666350325000069
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author Sean M. Carr, PhD
Ottis Scrivner, PhD
Katherine Elizabeth Hekman, MD, PhD
author_facet Sean M. Carr, PhD
Ottis Scrivner, PhD
Katherine Elizabeth Hekman, MD, PhD
author_sort Sean M. Carr, PhD
collection DOAJ
description Objective: Several decades of medical research have shown an intricate and definitive connection between dysfunctional endothelium and cardiovascular disorders, including atherosclerosis and peripheral artery disease (PAD). Initial investigations into endothelial cell (EC) physiology highlighted excretion of protein-based growth factors and their signaling pathways with highly specific targets. However, more recent research has focused on nonprotein metabolic signaling. Methods: A narrative review methodology was used. The review involved keyword searches of electronic databases, including Medline and ScienceDirect, conducted in March through October 2022. Review search terms included “endothelial cell metabolism,” “peripheral artery disease metabolism,” “angiogenesis metabolism,” and “endothelial cell metabolic regulation.” The search included primary research articles and subject matter narrative reviews. Abstracts were reviewed for English-language articles published between 2003 and 2022 and supplemented with targeted reference tracing. Results: Small-molecular-weight metabolites have been found to regulate key EC functions such as angiogenesis directly. More specifically, they impact EC behavior through control of energy production, de novo biomass synthesis, redox homeostasis, and production of gases like nitric oxide and hydrogen sulfide. Recent investigations targeting these metabolic pathways have yielded preliminary success in correcting undesirable endothelial dysfunction in atherosclerosis and PAD. Conclusions: Further investigations into therapeutic targeting of EC metabolism may yield novel approaches for treating PAD.
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spelling doaj-art-9d02f3bdb8484a1689dbd680cf86d1f82025-08-20T03:09:17ZengElsevierJVS - Vascular Science2666-35032025-01-01610028510.1016/j.jvssci.2025.100285Narrative review of endothelial cell metabolism and aberrations in atherosclerosis and peripheral artery diseaseSean M. Carr, PhD0Ottis Scrivner, PhD1Katherine Elizabeth Hekman, MD, PhD2Division of Vascular Surgery and Endovascular Therapy, Department of Surgery, Emory University School of Medicine and the Atlanta VA Health Care System, Atlanta, GADivision of Vascular Surgery and Endovascular Therapy, Department of Surgery, Emory University School of Medicine and the Atlanta VA Health Care System, Atlanta, GACorrespondence: Katherine Elizabeth Hekman, MD, PhD, Department of Surgery, Emory University School of Medicine, 1365 Clifton Rd NE Building A, Atlanta, GA 30322; Division of Vascular Surgery and Endovascular Therapy, Department of Surgery, Emory University School of Medicine and the Atlanta VA Health Care System, Atlanta, GAObjective: Several decades of medical research have shown an intricate and definitive connection between dysfunctional endothelium and cardiovascular disorders, including atherosclerosis and peripheral artery disease (PAD). Initial investigations into endothelial cell (EC) physiology highlighted excretion of protein-based growth factors and their signaling pathways with highly specific targets. However, more recent research has focused on nonprotein metabolic signaling. Methods: A narrative review methodology was used. The review involved keyword searches of electronic databases, including Medline and ScienceDirect, conducted in March through October 2022. Review search terms included “endothelial cell metabolism,” “peripheral artery disease metabolism,” “angiogenesis metabolism,” and “endothelial cell metabolic regulation.” The search included primary research articles and subject matter narrative reviews. Abstracts were reviewed for English-language articles published between 2003 and 2022 and supplemented with targeted reference tracing. Results: Small-molecular-weight metabolites have been found to regulate key EC functions such as angiogenesis directly. More specifically, they impact EC behavior through control of energy production, de novo biomass synthesis, redox homeostasis, and production of gases like nitric oxide and hydrogen sulfide. Recent investigations targeting these metabolic pathways have yielded preliminary success in correcting undesirable endothelial dysfunction in atherosclerosis and PAD. Conclusions: Further investigations into therapeutic targeting of EC metabolism may yield novel approaches for treating PAD.http://www.sciencedirect.com/science/article/pii/S2666350325000069Peripheral artery diseasePADEndothelial cellsEndothelial metabolismHydrogen sulfide
spellingShingle Sean M. Carr, PhD
Ottis Scrivner, PhD
Katherine Elizabeth Hekman, MD, PhD
Narrative review of endothelial cell metabolism and aberrations in atherosclerosis and peripheral artery disease
JVS - Vascular Science
Peripheral artery disease
PAD
Endothelial cells
Endothelial metabolism
Hydrogen sulfide
title Narrative review of endothelial cell metabolism and aberrations in atherosclerosis and peripheral artery disease
title_full Narrative review of endothelial cell metabolism and aberrations in atherosclerosis and peripheral artery disease
title_fullStr Narrative review of endothelial cell metabolism and aberrations in atherosclerosis and peripheral artery disease
title_full_unstemmed Narrative review of endothelial cell metabolism and aberrations in atherosclerosis and peripheral artery disease
title_short Narrative review of endothelial cell metabolism and aberrations in atherosclerosis and peripheral artery disease
title_sort narrative review of endothelial cell metabolism and aberrations in atherosclerosis and peripheral artery disease
topic Peripheral artery disease
PAD
Endothelial cells
Endothelial metabolism
Hydrogen sulfide
url http://www.sciencedirect.com/science/article/pii/S2666350325000069
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AT katherineelizabethhekmanmdphd narrativereviewofendothelialcellmetabolismandaberrationsinatherosclerosisandperipheralarterydisease