Serum Hepatocyte Growth Factor Concentration Is Associated With Blood Pressure in Subjects With Prehypertension

Abstract

Objective:Hepatocyte growth factor (HGF) is a pleiotropic factor that regulates cellular processes such as cell survival, proliferation, migration, and differentiation. Serum HGF concentration is associated with systolic blood pressure (BP) and is higher in hypertensive than in normotensive individuals, especially if complications of arterial hypertension are developed. Our aim was to determine the association of serum HGF concentration in subjects with prehypertension.Design and method:Data from 612 subjects (57,8% women, average age 41 years) was nalysed. After clinical examination, fasting blood and urine samples were drawn. HGF was measured using a commercial test. BP was measured according to the ESC/ESH guidelines. Based on BP values, subjects were divided into two groups: OBP - subjects with optimal blood pressure (BP < 120/80 mmHg, N = 295), and PHT (subjects with BP 120/80–140/90 mmHg N = 317).Results:Subjects with PHT were significantly older and had higher values of body mass index, waist circumference, serum total cholesterol levels, triglyceride levels, and fasting glucose levels (all p < 0.001). The prevalence of metabolic syndrome was significantly higher in PHT group (4.3% vs. 30.4%, p < 0,001). Serum HGF concentrations were higher in PHT subjects, but the difference was not significant (270.8 vs. 277.9 pg/ml, p = 0.651). Serum HGF concentration showed a significant positive correlation to systolic and diastolic BP in PHT (r = 0,226, p < 0,05 and r = 0,232, p < 0,01, respectively), but not in OBP group (p > 0.05).Conclusions:Serum HGF is associated with BP in prehypertensive subjects, but not in subjects with optimal BP. In our cohort, the correlation is more pronounced for diastolic blood pressure.

AICAR Ameliorates Non-Alcoholic Fatty Liver Disease via Modulation of the HGF/NF-κB/SNARK Signaling Pathway and Restores Mitochondrial and Endoplasmic Reticular Impairments in High-Fat Diet-Fed Rats

“…The present work investigated novel mechanisms underlying AICAR mitigation of NAFLD-associated oxido-inflammatory damage by modulating HGF/NF-κB signaling, regulating ER stress and mitochondrial dysfunction, and restoring metabolic homeostasis regardless of AMPK dependence. In humans, circulating high levels of HGF positively correlate with insulin resistance and glycemic status and were reported to be elevated in obesity, hypertension, and metabolic syndrome [ 15 , 16 ]. This is in line with the current finding that HFD-fed rats exhibited higher serum levels of HGF compared to the HFD + AICAR group.…”

“…In the context of NAFLD, gut Gram-negative bacteria and ROS induce toll-like receptor 4 (TLR4) stimulation. Furthermore, a heightened TLR4/NF-κB/TNF-α signaling pathway in hepatocytes and Kupffer cells release inflammatory cytokines and promote chronic inflammation [ 4 , 15 ]. Consistently, as observed herein, AICAR-ameliorated hepatic and systemic inflammatory response restored redox homeostasis.…”

“…The AMPK-independent action of AICAR on fatty acid oxidation in skeletal muscle has been also reported [ 53 ]. Irisin is derived from its precursor, fibronectin type III domain-containing protein 5 (FNDC5), which is under expressed in obesity and NAFLD [ 15 ]. Similarly, AICAR restores irisin levels in HFD-fed rats.…”

“…In this regard, lipid peroxidation products bind to hepatocyte proteins and initiate an immune response, neutrophil infiltration, and steatohepatitis, which lead to NF-κB activation in the liver [ 14 ]. NF-κB activation stimulates the transcription of hepatocyte growth factor (HGF), which is a hepatocyte mitogen elevated in sera of patients with NAFLD, obesity, hypertension, and metabolic syndrome [ 15 , 16 , 17 ]. HGF signaling is initiated by binding to its tyrosine kinase receptor (c-MET), followed by the phosphorylation and activation of downstream effectors such as phosphoinositide 3 kinase (PI3K), signal transducer and activator of transcription 3 (STAT3), mitogen-activated protein kinases (MAPK), and extracellular signal-regulated protein kinase (ERK).…”