The Interplay between Oxidative Stress and miRNAs in Obesity-Associated Hepatic and Vascular Complications

Abstract

Nowadays, the obesity pandemic is one of the most relevant health issues worldwide. This condition is tightly related to comorbidities such as non-alcoholic fatty liver disease (NAFLD) and cardiovascular diseases (CVDs), namely atherosclerosis. Dysregulated lipid metabolism and inflammation link these three diseases, leading to a subsequent increase of oxidative stress (OS) causing severe cellular damage. On the other hand, microRNAs (miRNAs) are short, single-stranded, non-coding RNAs that act as post-transcriptional negative regulators of gene expression, thus being involved in the molecular mechanisms that promote the development of many pathologies including obesity and its comorbidities. The involvement of miRNAs in promoting or opposing OS in disease progression is becoming more evident. Some miRNAs, such as miR-200a and miR.421, seem to play important roles in OS control in NAFLD. On the other hand, miR-92a and miR-133, among others, are important in the development of atherosclerosis. Moreover, since both diseases are linked to obesity, they share common altered miRNAs, being miR-34a and miR-21 related to OS. This review summarizes the latest advances in the knowledge about the mechanisms of oxidative stress (OS) generation in obesity-associated NAFLD and atherosclerosis, as well as the role played by miRNAs in the regulation of such mechanisms.

Circulating miRNAs Are Associated with the Systemic Extent of Atherosclerosis: Novel Observations for miR-27b and miR-146

“…Considering the miR-27b and miR-146 dysregulation observed in our study and their specific biological roles described in the aforementioned experimental studies [ 4 , 15 , 16 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 ], the extent of atherosclerosis in multiple territories and within each territory appears to be influenced by lipid metabolism and lipid accumulation in the vessel, and by the inflammatory response involving endothelial and monocyte–macrophage cells. These data reinforce the described mechanistic role of miRNAs in coupling lipid metabolism, endothelial dysfunction, inflammation, and atherosclerosis [ 42 , 43 , 44 , 45 , 46 ]. The interplay is complex, with each miRNA acting in multiple pathways and in different steps of a specific pathway, as post-transcriptional hubs.…”

Melatonin alleviates PM2.5‐induced glucose metabolism disorder and lipidome alteration by regulating endoplasmic reticulum stress

“…MiR‐200 family‐mediated gene regulation affected the maintenance of metabolic homeostasis, especially insulin resistance, obesity, and its comorbidities. High‐fat diet resulted in upregulation of miR‐200a in vivo and in vitro, which plays an irreplaceable role in the operational control system of metabolic liver disease 34 . Hepatic DNAJB9 drives anabolic bias to reduce steatosis and controls every circuit of glucose metabolism: insulin maturation, glycogen storage, and glucose release in liver cells 17 .…”

“…High-fat diet resulted in upregulation of miR-200a in vivo and in vitro, which plays an irreplaceable role in the operational control system of metabolic liver disease. 34 Hepatic DNAJB9 drives anabolic bias to reduce steatosis and controls every circuit of glucose metabolism: insulin maturation, glycogen storage, and glucose release in liver cells. 17 Transcriptome and proteomics results in this study both proved that PM 2.5 induced the increase of miR-200a-3p and the decrease of DNAJB9, and verified their targeted regulatory relationship for the first time (Figures 2-4).…”

MicroRNA‐34a in coronary heart disease: Correlation with disease risk, blood lipid, stenosis degree, inflammatory cytokines, and cell adhesion molecules

“…Coronary heart disease (CHD), mainly caused by atherosclerotic plaques as well as narrowness and occlusion of artery lumen, remains to be the leading cause of cardiovascular mortality with nearly 360 thousand deaths in the United States in 2018 1–4 . Moreover, CHD is often associated with other complications such as hypertension, diabetes mellitus (DM), and hyperuricemia, which increases difficulties in the management of CHD 5–7 .…”

“…Coronary heart disease (CHD), mainly caused by atherosclerotic plaques as well as narrowness and occlusion of artery lumen, remains to be the leading cause of cardiovascular mortality with nearly 360 thousand deaths in the United States in 2018. 1 , 2 , 3 , 4 Moreover, CHD is often associated with other complications such as hypertension, diabetes mellitus (DM), and hyperuricemia, which increases difficulties in the management of CHD. 5 , 6 , 7 Although many treatments have been applied (including anti‐ischemic, antiplatelet therapy, lipid lowering treatment, coronary revascularization, and exercise treatment), the prognosis of patients is still unsatisfying and CHD continues to bring large burden to patients such as reduced quality of life and enormous medical costs.…”