State of the art paper The role of G protein coupled receptor kinases in neurocardiovascular pathophysiology

Abstract

A b s t r a c tIn coronary artery disease the G protein related kinases (GRKs) play a role in desensitization of β-adrenoreceptors (AR) after coronary occlusion. Targeted deletion and lowering of cardiac myocyte GRK-2 decreases the risk of postischemic heart failure (HF). Studies carried out in humans confirm the role of GRK-2 as a marker for the progression of HF after myocardial infarction (MI). The level of GRK-2 could be an indicator of β-AR blocker efficacy in patients with acute coronary syndrome. Elevated levels of GRK-2 are an early ubiquitous consequence of myocardial injury. In hypertension an increased level of GRK-2 was reported in both animal models and human studies. The role of GRKs in vagally mediated disorders such as vasovagal syncope and atrial fibrillation remains controversial. The role of GRKs in the pathogenesis of neurocardiological diseases provides an insight into the molecular pathogenesis process, opens potential therapeutic options and suggests new directions for scientific research.K Ke ey y w wo or rd ds s: : autonomic, sympathetic, vagal, molecular signaling pathway. Neurocardiovascular pathophysiology: sympathetic versus vagally mediated disordersNeural control of the cardiovascular (CV) system is an integral part of CV physiology and consequently a part of CV pathological mechanisms. Two fundamental parts of the autonomic nervous system -the sympathetic and parasympathetic (vagal) components -play a role in the development and initiation of the pathological process. The classification of neurocardiological disorders by Goldstein [1] is as follows: 1) Sympathetic disorders -diseases in which activation of the catecholamine system worsens an independent pathological state (coronary artery disease, arrhythmias as long QT syndrome, sudden death, heart failure (HF)) as well as diseases in which abnormal catecholaminergic function is etiologic (sympathetic neurocirculatory failure, hypertension, cardiac necrosis and cardiomyopathy), and 2) Vagally mediated disorders -both neurally mediated syncope (vasovagal syncope, carotid sinus hypersensitivity) and vagally mediated atrial fibrillation. Neural regulation of the CV system can be studied by using different techniques [2][3][4][5][6][7][8]. G protein related kinases (GRKs) exist in 7 isoforms -GRK 1-7. They are serine-threonine protein kinases that are C Co or rr re es sp po on nd di in ng g a au ut th ho or r: :

The Evolving Impact of G Protein-Coupled Receptor Kinases in Cardiac Health and Disease

“…In addition, increased levels of GRK2 have also been reported in other human studies of disease states (reviewed in Refs. 14,27). In animal models of cardiac injury, GRK2 upregulation is one of the first cardiac molecular changes seen (159,273).…”

Calcium sensitive receptor and claudin-14 expression in kidney tissues of two kidney stone models

“…The urine is relatively supersaturated to induce the formation of calcium-containing stones [6]. In recent years, with the study of G protein coupled receptors, new treatments are gradually being discovered [7]. CaSR is a G protein-coupled receptor that has been found to be significantly associated with urinary calcium excretion in recent years.…”

Acupuncture, autonomic nervous system and biophysical origin of acupuncture system

“…If that is so, than modeling physiological processes during therapeutic responses of acupuncture might be significant for indication on nature of AS (jīngluò). Bearing in mind that ANS is one of the most significant systems that regulates organic func-Matić Z, Bojić T. Vojnosanit Pregl 2020; 77(1): 79-86. tions [8][9][10][11][12][13][14][15] it follows that characteristics of ANS exactly should be in focus of evaluation before and after acupuncture therapies. Therefore, it is first necessary to explore and summarize recent research about the influence of acupuncture on ANS.…”