Treg cells depletion is a mechanism that drives microvascular dysfunction in mice with established hypertension.

Biochim Biophys Acta Mol Basis Dis

Department of Physiological Sciences, EVMS, Norfolk, VA 23501, USA. Electronic address:

Published: February 2019

Background: Microvascular dysfunction is a major complication in hypertensive patients. We previously reported that CD4CD25 T regulatory cells (Treg) play an important preventive role in hypertension-induced vascular dysfunction. However, whether Treg cells therapy and autophagy inhibition could rescue Treg cells survival and microvascular function in established hypertension is an important question that remained unanswered.

Methods & Results: Here we showed that Treg cells from mice model of established hypertension displayed an enhanced apoptotic rate, which was rescued with Treg cells transfer and autophagy inhibition. We also showed increased autophagy in mesenteric resistance artery (MRA) in mice with established hypertension. Importantly, the inhibition of autophagy or one single transfer of Treg cells into mice with established hypertension improved the microvascular function independently of high blood pressure. The protection involves the modulation of interleukin-10 (IL-10), inflammation, endoplasmic reticulum (ER) stress, oxidative stress, Akt, and eNOS.

Conclusions: The present study suggests that Treg cells survival is regulated by autophagy. Also, Treg cells as a cellular therapy aimed at rescuing the microvascular function through an autophagy-dependent mechanism and independently of arterial blood pressure lowering effects. Because our mouse model of established hypertension mimics the clinical situation, our results have the potential for new therapeutic approaches that involve the manipulation of Treg cells and autophagy to overcome established hypertension-induced cardiovascular complications.

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Source
http://dx.doi.org/10.1016/j.bbadis.2018.10.031DOI Listing

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