Recent advances in molecular biology of metabolic syndrome pathophysiology: endothelial dysfunction as a potential therapeutic target

Abstract

Current advances in molecular pathobiology of endotheliocytes dysfunctions are promising in finding the pathogenetic links to the emergence of insulin resistance syndrome. Physiologically, human organism homeostasis is strictly controlled to maintain metabolic processes at the acquainted level. Many factors are involved in maintaining these physiological processes in the organism and any deviation is undoubtedly accompanied by specific pathologies related to the affected process. Fortunately, the body’s defense system can solve and compensate for the impaired function through its multi-level defense mechanisms. The endothelium is essential in maintaining this homeostasis through its ability to modulate the metabolic processes of the organism. Pathological activity or impairment of physiological endothelium function seems directly correlated to the emergence of metabolic syndrome. The most accepted hypothesis is that endothelium distribution is due to endoplasmic reticulum stress and unfolded protein response development, which includes inhibition of long non-coding RNAs expression, cytokines disbalance, Apelin dysregulation, glycocalyx degradation, and specific microparticles. Clinically, the enhancement or restoration of normal endothelial cells can be a target for novel therapeutic strategies since the distribution of its physiological activity impairs homeostasis and results in the progression of metabolic syndrome, and induction of its physiological activity can ameliorate insulin resistance syndrome. Novel insights on the molecular mechanisms of endothelial cell dysfunction are concisely represented in this paper to enhance the present therapeutic tactics and advance the research forward to find new therapeutic targets.

The Metabolic Syndrome, a Human Disease

“…The relationship of MS with inflammation independently affects most of its components despite its global effects [366,367]. These processes occur at a lower structural level, closer to molecules than to global organ function, i.e., than the classical physiology definition described above and of comfortably accepted reference [358,368].…”

“…Inflammation is assumed to be a main process driving MS; however, this generally accepted (global) idea [18,28,30] is in fact ill defined. "Inflammation" is a clinical term that includes a wide array of situations of altered homeostasis through quite different pathways and mechanisms [86,358]. In MS, inflammation (latu senso) is at the root of many of its collection of disorders [18,359].…”

Pengaruh Ekstrak Buah Naga Merah (Hylocereus polyrhizus) Terhadap Kadar LDL pada Tikus Wistar Model Sindrom Metabolik

“…Asupan HFFD juga meningkatkan partikel apolipoprotein B yang diikuti dengan peningkatan laju sintesis VLDL dan LDL dalam hepar (Ning et al, 2015). Kadar LDL yang tinggi dapat merangsang terjadinya stres oksidatif dan reaksi inflamasi endotel dengan cara meningkatkan kadar reactive oxygen species (ROS) dan menurunkan sintesis nitric oxide (Marzoog, 2022).…”

Tree of life: endothelial cell in norm and disease, the good guy is a partner in crime!

“…Furthermore, EC can modify their metabolic activities, probably, through modulation of active substance releasing, according to the triggered endothelial plasma membrane receptor [ 11 - 13 ]. Usually, the transient receptor potential (TRP) and G-coupled-protein receptor play a leading role in triggering the intracellular signaling cascade, later activate specific Ca +2 channels or K + channels as well as probably promote specific gene expression or repressions such as pro-inflammatory genes that encode for cytokines, via activating the nuclear factor-κB or mitogen-activated protein kinase pathways [ 14 , 15 ].…”