Transforming Growth Factor-β Protects against Inflammation-Related Atherosclerosis in South African CKD Patients

Abstract

Background Transforming growth factor-β (TGF-β) may inhibit the development of atherosclerosis. We evaluated serum levels of TGF-β isoforms concurrently with serum levels of endotoxin and various inflammatory markers. In addition, we determined if any association exists between polymorphisms in the TGF-β1 gene and atherosclerosis in South African CKD patients. Methods We studied 120 CKD patients and 40 healthy controls. Serum TGF-β1, TGF-β2, TGF-β3, endotoxin, and inflammatory markers were measured. Functional polymorphisms in the TGF-β1 genes were genotyped using a polymerase chain reaction-sequence specific primer method and carotid intima media thickness (CIMT) was assessed by B-mode ultrasonography. Results TGF-β isoforms levels were significantly lower in the patients with atherosclerosis compared to patients without atherosclerosis (p<0.001). Overall, TGF-β isoforms had inverse relationships with CIMT. TGF-β1 and TGF-β2 levels were significantly lower in patients with carotid plaque compared to those without carotid plaque [TGF-β1: 31.9 (17.2 – 42.2) versus 45.9 (35.4 – 58.1) ng/ml, p=0.016; and TGF-β2: 1.46 (1.30 – 1.57) versus 1.70 (1.50 – 1.87) ng/ml, p=0.013]. In multiple logistic regression, age, TGF-β2, and TGF-β3 were the only independent predictors of subclinical atherosclerosis in CKD patients [age: odds ratio (OR), 1.054; 95% confidence interval (CI): 1.003 – 1.109, p=0.039; TGF-β2: OR, 0.996; 95% CI: 0.994–0.999, p=0.018; TGF-β3: OR, 0.992; 95% CI: 0.985–0.999, p=0.029). TGF-β1 genotypes did not influence serum levels of TGF-β1 and no association was found between the TGF-β1 gene polymorphisms and atherosclerosis risk. Conclusion TGF-β isoforms seem to offer protection against the development of atherosclerosis among South African CKD patients.

Silencing circular ANRIL protects HK-2 cells from lipopolysaccharide-induced inflammatory injury through up-regulating microRNA-9

“…The most common concurrent cardiovascular disorder is characterized by accelerated systemic inflammation in confirmed CKD process [6,7]. Renal tubular inflammatory disease, one of the pathological manifestations of the chronic inflammatory response, is prevailing in patients with coexisting CKD and atherosclerosis by stimulating inflammatory factors and activating oxidative stress [8]. Therefore, it is worthy to find molecular biomarkers that can fight against inflammation or prevent atherosclerosis, thus contributing to the clinical therapeutic method of CKD.…”

Role of Circular RNA in Kidney-Related Diseases

“…Furthermore, kidney-related diseases can interevolve to each other. Nephrectomy due to RCC may impair kidney function, AKI likely contributes to the development and progression of CKD, AKI is also one of the major complications in CKD ( Uchino et al, 2005 ; He et al, 2017 ; Hassan et al, 2018 ). And cir-ATK3 takes part in RCC and AKI, whether exists a particular circRNA that regulates the progression of multiple kidney-related diseases simultaneously need to be confirmed.…”

Heme Induces Endoplasmic Reticulum Stress (HIER Stress) in Human Aortic Smooth Muscle Cells

“…A body of evidence suggest that TGFβ promotes plaque stability and reduces atherosclerotic plaque size ( Bobik, 2006 ; Chen et al, 2006 , 2016 ; Bot et al, 2009 ; Reifenberg et al, 2012 ; Hassan et al, 2018 ). In addition, inhibition of TGFβ signaling accelerates atherosclerosis, decreases collagen synthesis and induces hemorrhages and iron deposition ( Mallat et al, 2001 ; Lutgens et al, 2002 ).…”

“…Endoplasmic reticulum stress was shown to suppress the expression of TGFβ and downstream product collagen type I. TGFβ enhances plaque stability, reduces atherosclerotic plaque size ( Bobik, 2006 ; Chen et al, 2006 , 2016 ; Bot et al, 2009 ; Reifenberg et al, 2012 ; Hassan et al, 2018 ), and is limitedly present in advanced atherosclerotic plaques ( Grainger et al, 1995 ; Bobik et al, 1999 ; McCaffrey et al, 1999 ).…”