Autophagy as an emerging therapeutic target for age-related vascular pathologies

ABSTRACT

Introduction: The incidence of age-related vascular diseases such as arterial stiffness, hypertension and atherosclerosis, is rising dramatically and is substantially impacting healthcare systems. Mounting evidence suggests that there is an important role for autophagy in maintaining (cardio)vascular health. Impaired vascular autophagy has been linked to arterial aging and the initiation of vascular disease.

Areas covered: The function and implications of autophagy in vascular smooth muscle cells and endothelial cells are discussed in healthy blood vessels and arterial disease. Furthermore, we discuss current treatment options for vascular disease and their links with autophagy. A literature search was conducted in PubMed up to October 2019.

Expert opinion: Although the therapeutic potential of inducing autophagy in age-related vascular pathologies is considerable, several issues should be addressed before autophagy induction can be clinically used to treat vascular disease. These issues include uncertainty regarding the most effective drug target as well as the lack of potency and selectivity of autophagy inducing drugs. Moreover, drug tolerance or autophagy mediated cell death have been reported as possible adverse effects. Special attention is required for determining the cause of autophagy deficiency to optimize the treatment strategy.

KEYWORDS:

• Atherosclerosis
• autophagy
• endothelial cell
• hypertension
• smooth muscle cell
• vascular stiffening

Article highlights

• Autophagy plays a major role in the phenotype and function of endothelial cells and vascular smooth muscle cells, which are the two most abundant cell types in blood vessels.

• Vascular aging is associated with a decline in autophagy. Induction of autophagy attenuates vascular stiffness and the development of hypertension.

• Autophagy is present in all major cell types of atherosclerotic plaques (endothelial cells, vascular smooth muscle cells, macrophages) and promotes plaque stability.

• Interpretation of data after autophagy induction is difficult in the context of aged vessels because autophagy has a combined effect on aging and vascular function.

• Pharmacological stimulation of autophagy could be an important strategy in the treatment of vascular disease.

This box summarizes key points contained in the article.

Acknowledgments

The authors are grateful to Dr. Bronwen Martin for critical reading of the manuscript.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

The work of the authors was supported by the Fund for scientific Research (FWO)-Flanders (grant N° G.0412.16N) and the University of Antwerp (BOF).