Therapeutic potential of blood flow mimetic compounds in preventing endothelial dysfunction and atherosclerosis

Abstract

Endothelial cells (ECs), as one of the most important types of vascular cells, line the innermost layer of all blood vessels throughout human body and regulate vascular tone and homeostasis. ECs are constantly exposed to different types of shear stress (one form of mechanical forces) generated by the flowing blood. Various mechanosensing molecules or complexes existing on EC membrane serve as versatile sensors (termed as mechanosensors) of different patterns and pattern alternation of blood flow. Via these mechanosensors, ECs sense and transduce flow-induced biomechanical signal into different mechano-transduction pathways, leading to altered expression/activity of mechanosensitive transcription factors (TFs), epigenetic modification enzymes, non-coding RNAs, and genes, thereby generating biological responses (i.e., the regulation of endothelial function). Dysfunction of ECs (i.e., endothelial dysfunction) represents one of the most important pathomechanisms for atherosclerosis, hypertension and diabesity. Emerging studies have demonstrated that pharmacological modulators of mechanosensors/TFs/enzymes improve endothelial dysfunction and reduce the incidence of experimental atherosclerosis. Here, I overviewed the important role of endothelial mechanoregulators in vascular endothelium, highlighting the potential of blood flow mimetic compounds to treat endothelial dysfunction and associated atherosclerotic cardiovascular diseases.

Keywords: Biomechanics; Endothelial function; GSK1016790A (PubChem CID: 23630211); Gambogic acid (PubChem CID: 9852185); Liraglutide (PubChem CID: 16134956); Mechanobiology; Mechanosensor; Metformin (PubChem CID:4091); SAHA (PubChem CID: 5311); Shear stress; Simvastatin (PubChem CID: 54454); Sulforaphane (PubChem CID: 5350); Tannic acid (PubChem CID: 16129778); Therapeutics; Verteporfin (PubChem CID: 11980904); Yoda 1 (PubChem CID: 2746822).