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The pathophysiology of peripheral arterial disease: rational targets for drug intervention
1Falk Cardiovascular Research Center, Stanford University School of Medicine 94305-5246, USA.
Insights
Peripheral arterial disease (PAD) stems from atherosclerosis, impacting endothelial function and microcirculation. Emerging therapies aim to reverse atherosclerosis, inhibit thrombosis, and improve tissue perfusion for PAD patients.
Area of Science:
- Vascular Biology
- Cardiovascular Medicine
- Pharmacotherapy
Background:
- Peripheral arterial disease (PAD) is most commonly caused by atherosclerosis.
- Atherosclerosis initiates with endothelial dysfunction driven by risk factors like hypercholesterolemia, diabetes, hypertension, and smoking.
- Chronic PAD leads to microcirculation obstruction and tissue injury.
Purpose of the Study:
- To review current understanding of PAD vascular biology.
- To discuss novel therapeutic strategies for PAD based on biological insights.
- To outline future directions for pharmacotherapy in managing PAD.
Main Methods:
- Review of current literature on PAD pathogenesis.
- Analysis of emerging therapeutic targets and agents in clinical trials.
- Synthesis of insights into vascular biology and microcirculation.
Main Results:
- Atherosclerosis progression is linked to endothelial dysfunction and microvascular changes.
- New therapies are being developed targeting various aspects of PAD.
- Future treatments will likely possess multiple attributes to combat PAD comprehensively.
Conclusions:
- Understanding PAD vascular biology is crucial for developing effective treatments.
- Pharmacotherapy for PAD is evolving towards multi-targeted agents.
- Future PAD therapies aim to reverse atherosclerosis, prevent thrombosis, induce angiogenesis, and improve tissue health.
Abstract:
The most common cause of peripheral arterial disease (PAD) is atherosclerosis, which begins with an alteration in endothelial biology due to hypercholesterolemia, diabetes mellitus, hypertension, tobacco use, elevated levels of lipoprotein(a) or homocystinemia. With chronic and severe arterial disease, changes begin to occur in the microcirculation, including obstruction at the microvascular level and tissue injury. Based on insights into the vascular biology of PAD, new therapies have been developed and are at various stages of clinical trials. Future pharmacotherapy for PAD will include agents that have one or more of the following attributes; (1) reduce, or even reverse, the progression of atherosclerosis; (2) inhibit plaque rupture; (3) inhibit thrombosis by a novel mechanism; (4) induce angiogenesis; (5) reverse microvascular derangements; (6) affect blood rheology; and (7) enhance skeletal muscle's ability to use available nutrients.