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Vascular autophagy in health and disease

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Abstract

Homeostasis is maintained within organisms through the physiological recycling process of autophagy, a catabolic process that is intricately involved in the mobilization of nutrients during starvation, recycling of cellular cargo, as well as initiation of cellular death pathways. Specific to the cardiovascular system, autophagy responds to both chemical (e.g. free radicals) and mechanical stressors (e.g. shear stress). It is imperative to note that autophagy is not a static process, and measurement of autophagic flux provides a more comprehensive investigation into the role of autophagy. The overarching themes emerging from decades of autophagy research are that basal levels of autophagic flux are critical, physiological stressors may increase or decrease autophagic flux, and more importantly, aberrant deviations from basal autophagy may elicit detrimental effects. Autophagy has predominantly been examined within cardiac or vascular smooth muscle tissue within the context of disease development and progression. Autophagic flux within the endothelium holds an important role in maintaining vascular function, demonstrated by the necessary role for intact autophagic flux for shear-induced release of nitric oxide however the underlying mechanisms have yet to be elucidated. Within this review, we theorize that autophagy itself does not solely control vascular homeostasis, rather, it works in concert with mitochondria, telomerase, and lipids to maintain physiological function. The primary emphasis of this review is on the role of autophagy within the human vasculature, and the integrative effects with physiological processes and diseases as they relate to the vascular structure and function.

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Abbreviations

AMPK:

5′ Adenosine monophosphate-activated protein kinase

CAD:

Coronary artery disease

eNOS:

Endothelial nitric oxide synthase

FMD:

Flow-mediated dilation

SIRT:

Sirtuins

H2O2 :

Hydrogen peroxide

LC3:

Microtubule-associated protein 1A/1B-light chain 3

mTOR:

Mammalian target of rapamycin

NO:

Nitric oxide

ROS:

Reactive oxygen species

SOD:

Superoxide dismutase

TERT:

Telomerase reverse transcriptase

TFEB:

Transcription factor EB

VSM:

Vascular smooth muscle

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Funding

This work was supported by the National Institutes of Health Grants T32GM089586 and AHA 20POST35050017 (W.E.H); R01-HL-133029 (A.M. Beyer); R01-HL-135901-01 (D.D. Gutterman).

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  1. Department of Medicine, Cardiovascular Center, Medical College of Wisconsin, 8701 West Watertown Plank Road, Milwaukee, WI, 53213, USA

    William E. Hughes, Andreas M. Beyer & David D. Gutterman

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  1. William E. Hughes
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  2. Andreas M. Beyer
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  3. David D. Gutterman
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Correspondence to William E. Hughes.

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Hughes, W.E., Beyer, A.M. & Gutterman, D.D. Vascular autophagy in health and disease. Basic Res Cardiol 115, 41 (2020). https://doi.org/10.1007/s00395-020-0802-6

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