Adding a “Notch” to Cardiovascular Disease Therapeutics: A MicroRNA-Based Approach

Abstract

Dysregulation of the Notch pathway is implicated in the pathophysiology of cardiovascular diseases (CVDs), but, as of today, therapies based on the re-establishing the physiological levels of Notch in the heart and vessels are not available. A possible reason is the context-dependent role of Notch in the cardiovascular system, which would require a finely tuned, cell-specific approach. MicroRNAs (miRNAs) are short functional endogenous, non-coding RNA sequences able to regulate gene expression at post-transcriptional levels influencing most, if not all, biological processes. Dysregulation of miRNAs expression is implicated in the molecular mechanisms underlying many CVDs. Notch is regulated and regulates a large number of miRNAs expressed in the cardiovascular system and, thus, targeting these miRNAs could represent an avenue to be explored to target Notch for CVDs. In this Review, we provide an overview of both established and potential, based on evidence in other pathologies, crosstalks between miRNAs and Notch in cellular processes underlying atherosclerosis, myocardial ischemia, heart failure, calcification of aortic valve, and arrhythmias. We also discuss the potential advantages, as well as the challenges, of using miRNAs for a Notch-based approach for the diagnosis and treatment of the most common CVDs.

Developmental Regulation and Functional Prediction of microRNAs in an Expanded Fasciola hepatica miRNome

“…For example, miRNA mimics or inhibitors could be used to manipulate transcript expression alongside or in place of RNA interference (RNAi) methods. These new approaches could be useful for laboratory-based functional genomics, or even as new avenues for control [miRNAs have been suggested as therapeutic targets in various human diseases ( Marracino et al., 2021 ; Shi et al., 2021 ; Smit-McBride and Morse, 2021 )]. Furthermore, inhibiting EV release from helminths would conceivably prevent delivery of miRNAs (and other bioactive molecules) to host immune cells.…”

Fluoxetine attenuates apoptosis in early brain injury after subarachnoid hemorrhage through Notch1/ASK1/p38 MAPK signaling pathway

“…Notch pathway dysregulation has been reported in various neurological conditions, such as ischemia. Notch1 overexpression has specifically been linked with disease severity, and its pharmacological regulation has been reported as a possible therapeutic target [ 41 , 42 ]. In our current findings, Notch1 signaling pathways and their associated proteins, including Hes 1, Hes 5, and Jagged 5, were upregulated following the Fluoxetine treatment.…”

Cardiac Remodeling After Myocardial Infarction: Functional Contribution of microRNAs to Inflammation and Fibrosis

“…miRNA-based therapeutics have been proven to be effective for treating cardiovascular diseases ( 1 , 96 ). Since miRNAs can regulate multiple genes using different signaling pathways, they have a great potential as novel therapeutic agents; therapeutic strategies based on miRNA modulation have been widely utilized in angiogenesis, atherosclerosis, ischemic injury, vascular remodeling, hypertrophy, and fibrosis ( 97 , 98 ).…”