Diabetic atherosclerosis: is there a role for the hypoxia-inducible factors?

Daniela Pirri,Paul C Evans,Maria Fragiadaki

doi:10.1042/bsr20200026

Abstract

Atherosclerosis is a major cause of mortality worldwide and is driven by multiple risk factors, including diabetes. Diabetes is associated with either an insulin deficiency in its juvenile form or with insulin resistance and obesity in Type 2 diabetes mellitus, and the latter is clustered with other comorbidities to define the metabolic syndrome. Diabetes and metabolic syndrome are complex pathologies and are associated with cardiovascular risk via vascular inflammation and other mechanisms. Several transcription factors are activated upon diabetes-driven endothelial dysfunction and drive the progression of atherosclerosis. In particular, the hypoxia-inducible factor (HIF) transcription factor family is a master regulator of endothelial biology and is raising interest in the field of atherosclerosis. In this review, we will present an overview of studies contributing to the understanding of diabetes-driven atherosclerosis, integrating the role of HIF in this disease with the knowledge of its functions in metabolic syndrome and diabetic scenario.

Highlights

Diabetes is a risk factor for cardiovascular disease (CVD), which causes around 17 millions deaths each year [1]
Metabolic syndrome is characterised by the co-existence of raised blood pressure, insulin resistance, obesity and dyslipidaemia, hypertriglyceridaemia and reduced ratio of high density lipoproteins (HDL) to low density lipoproteins (LDL)
Diabetes type 2 increases fatty acid metabolism against the utilization of glucose through glycolysis; this leads to a reduction of succinate content which decreases HIF1-α levels in diabetic hearts [100]

Summary

Introduction

Diabetes is a risk factor for cardiovascular disease (CVD), which causes around 17 millions deaths each year [1]. Multiple transcription factors contribute to atherosclerosis progression and some of these have key roles in controlling metabolic syndrome. Diabetes-induced activation of protein kinase-β (PKC-β) increases production of AGE from the polyol pathway and leads to accelerated atherosclerosis, reduced insulin-stimulated eNOS production and increased expression of the vasoconstrictive molecule, ET-1 [52,53].

Results

Conclusion