MicroRNAs As Master Regulators of Atherosclerosis: From Pathogenesis to Novel Therapeutic Options

Hosen, Mohammed Rabiul; Goody, Philip Roger; Zietzer, Andreas; Nickenig, Georg; Jansen, Felix

doi:10.1089/ars.2020.8107

Cited by 29 publications

(32 citation statements)

References 186 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently omics technologies and computational approaches have become intriguing tools and approaches for drug discovery, making use of gene expression data. Exploiting the systems biology approaches in several studies [ 39 , 40 , 41 , 42 ], master regulators have been reported as potential therapeutic targets. By definition, master regulators are molecules that are located at the top of the hierarchy involved in the transcriptomic regulation, where the nodes tend to converge after certain upstream steps [ 43 ].…”

Section: Introductionmentioning

confidence: 99%

Computational Identification of Master Regulators Influencing Trypanotolerance in Cattle

Rajavel

Schmitt

Gültaş

2021

IJMS

View full text Add to dashboard Cite

African Animal Trypanosomiasis (AAT) is transmitted by the tsetse fly which carries pathogenic trypanosomes in its saliva, thus causing debilitating infection to livestock health. As the disease advances, a multistage progression process is observed based on the progressive clinical signs displayed in the host’s body. Investigation of genes expressed with regular monotonic patterns (known as Monotonically Expressed Genes (MEGs)) and of their master regulators can provide important clue for the understanding of the molecular mechanisms underlying the AAT disease. For this purpose, we analysed MEGs for three tissues (liver, spleen and lymph node) of two cattle breeds, namely trypanosusceptible Boran and trypanotolerant N’Dama. Our analysis revealed cattle breed-specific master regulators which are highly related to distinguish the genetic programs in both cattle breeds. Especially the master regulators MYC and DBP found in this study, seem to influence the immune responses strongly, thereby susceptibility and trypanotolerance of Boran and N’Dama respectively. Furthermore, our pathway analysis also bolsters the crucial roles of these master regulators. Taken together, our findings provide novel insights into breed-specific master regulators which orchestrate the regulatory cascades influencing the level of trypanotolerance in cattle breeds and thus could be promising drug targets for future therapeutic interventions.

show abstract

Section: Introductionmentioning

confidence: 99%

Computational Identification of Master Regulators Influencing Trypanotolerance in Cattle

Rajavel

Schmitt

Gültaş

2021

IJMS

View full text Add to dashboard Cite

show abstract

“…MiRNAs by interactions with mRNAs impact protein synthesis; hence, they play a significant role in developing numerous diseases. The effect of harmful stimuli and the influence of miRNA may be the cause of atherogenesis [ 67 ]. It has been found that miRNAs are regulated in different stages of atherosclerosis, from activation and proliferation to cellular senescence.…”

Section: Biomarkersmentioning

confidence: 99%

Recognized and Potentially New Biomarkers—Their Role in Diagnosis and Prognosis of Cardiovascular Disease

et al. 2021

View full text Add to dashboard Cite

Atherosclerosis and its consequences are the leading cause of mortality in the world. For this reason, we have reviewed atherosclerosis biomarkers and selected the most promising ones for review. We focused mainly on biomarkers related to inflammation and oxidative stress, such as the highly sensitive C-reactive protein (hs-CRP), interleukin 6 (IL-6), and lipoprotein-associated phospholipase A2 (Lp-PLA2). The microRNA (miRNA) and the usefulness of the bone mineralization, glucose, and lipid metabolism marker osteocalcin (OC) were also reviewed. The last biomarker we considered was angiogenin (ANG). Our review shows that due to the multifactorial nature of atherosclerosis, no single marker is known so far, the determination of which would unambiguously assess the severity of atherosclerosis and help without any doubt in the prognosis of cardiovascular risk.

show abstract

“…MiRNA inhibitors (also known as antagomiRs) that can inhibit miRNA function in mouse, primate and human cell models of diseases are currently being studied as possible pharmacological agents for regulating gene function. It is possible to inhibit siRNAs using specific blockers for target sites or using miRNA sponges that reduce the number of target sites available for binding ( 74 ).…”

Section: Mitochondria-targeting Gene Therapy For Atherosclerosismentioning

confidence: 99%

Atherosclerosis as Mitochondriopathy: Repositioning the Disease to Help Finding New Therapies

Shemiakova

Ivanova

et al. 2021

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

Atherosclerosis is a complex pathology that involves both metabolic dysfunction and chronic inflammatory process. During the last decade, a considerable progress was achieved in describing the pathophysiological features of atherosclerosis and developing approaches that target the abnormal lipid metabolism and chronic inflammation. However, early events in the arterial wall that initiate the disease development still remain obscure. Finding effective therapeutic targets in these early processes would allow developing methods for disease prevention and, possibly, atherosclerotic plaque regression. Currently, these early events are being actively studied by several research groups. One of the processes that are being investigated is the development of mitochondrial dysfunction, which was demonstrated to be present in the affected areas of the arterial wall. Detection and characterization of mitochondrial dysfunction associated with several chronic human disorders was made possible by the improved methods of studying mitochondrial biology and detecting mitochondrial DNA (mtDNA) mutations. It was found to be involved in several key atherogenic processes, such as oxidative stress, chronic inflammation, and intracellular lipid accumulation. Mitochondrial dysfunction can occur in all types of cells involved in the pathogenesis of atherosclerosis: monocytes and macrophages, smooth muscle cells, lymphocytes, and the endothelial cells. However, therapies that would specifically target the mitochondria to correct mitochondrial dysfunction and neutralize the defective organelles are still remain to be developed and characterized. The aim of this review is to outline the prospects for mitochondrial therapy for atherosclerosis. We discuss mechanisms of mitochondria-mediated atherogenic processes, known mitochondria-targeting therapy strategies, and novel mitochondria-targeting drugs in the context of atherosclerosis.

show abstract

MicroRNAs As Master Regulators of Atherosclerosis: From Pathogenesis to Novel Therapeutic Options

Cited by 29 publications

References 186 publications

Computational Identification of Master Regulators Influencing Trypanotolerance in Cattle

Computational Identification of Master Regulators Influencing Trypanotolerance in Cattle

Recognized and Potentially New Biomarkers—Their Role in Diagnosis and Prognosis of Cardiovascular Disease

Atherosclerosis as Mitochondriopathy: Repositioning the Disease to Help Finding New Therapies

Contact Info

Product

Resources

About