Key result
Small-molecular-weight metabolites regulate key endothelial cell functions, and targeting these metabolic pathways has yielded preliminary success in correcting endothelial dysfunction in atherosclerosis and peripheral artery disease.
Why the study?
Recent research has shifted focus from protein-based signaling to nonprotein metabolic signaling in endothelial cell dysfunction associated with atherosclerosis and peripheral artery disease.
Further investigations into therapeutic targeting of endothelial cell metabolism, including small-molecular-weight metabolites and gasotransmitters, may yield novel approaches for treating peripheral artery disease.
Answers are grounded in this paper and cite their sources.
Nonprotein metabolic EC signaling extends protein-focused models of endothelial dysfunction; leaves open therapeutic targets in atherosclerosis and PAD.
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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Carr et al. (2025) conducted a review in Atherosclerosis and peripheral artery disease. Endothelial cell metabolism targeting was evaluated. Small-molecular-weight metabolites regulate key endothelial cell functions, and targeting these metabolic pathways has yielded preliminary success in correcting endothelial dysfunction in atherosclerosis and peripheral artery disease.
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