Renal denervation significantly attenuates cardiorenal fibrosis in rats with sustained pressure overload.
To investigate the effects of renal denervation (RDN) on comprehensive cardiac and renal fibrosis in cardiomyopathy. Five weeks after successful transverse aortic constriction (TAC)-induced cardiomyopathy model building, Sprague-Dawley rats were randomly assigned to three groups: (1) RDN, (2) sham, and (3) losartan. Sham TAC rats served as control group. Compared with control, TAC groups showed a significant decrease in left ventricle ejection fraction and increase in ventricular septum thickness and left atrium diameter on echocardiography after 5 weeks. At 10 weeks post-TAC, venous blood samples were collected for fibrosis biochemical assay. Heart and kidney samples were also harvested for fibrosis pathophysiological detection. Cardiac and renal fibrosis quantity results showed that, compared with sham group, collagen volume fraction was significantly decreased in RDN group more than in losartan group. Biochemical parameters such as tumor necrosis factor α, aldosterone, and B-type natriuretic peptide levels as well as biomarkers for fibrosis such as procollagen type I N-terminal propeptide and procollagen type III N-terminal propeptide concentrations were significantly decreased in RDN group in comparison with sham. In addition, compared with sham group, left ventricle tissue protein expression of transforming growth factor-β1 and angiotensin II type I receptor was downregulated, and angiotensin-converting enzyme 2 was upregulated in RDN but not in losartan group. RDN significantly attenuates cardiac and renal fibrosis in cardiomyopathy. Differing from losartan, which only has angiotensin II type I receptor inhibition effects, RDN comprehensively suppresses cardiac and renal fibrogenesis through multiple pathways.
Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
Qian
Q
Liu
Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
Dasheng
D
Lu
Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
Shengchan
S
Wang
Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
Kai
K
Wang
Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
Qi
Q
Zhang
Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
Ying
Y
Wang
Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
Ping
P
Fang
Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
Zhenzhen
Z
Li
Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
Jie
J
Geng
Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China. Electronic address: qjshan@njmu.edu.cn.
Qijun
Q
Shan
D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000097:blood; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D000818:Animals; D015415:Biomarkers / Q000097:blood; D009202:Cardiomyopathies / Q000097:blood / Q000188:drug therapy / Q000601:surgery*; D004195:Disease Models, Animal; D005355:Fibrosis; D006325:Heart Atria / Q000187:drug effects / Q000378:metabolism; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000294:innervation / Q000473:pathology*; D019808:Losartan / Q000627:therapeutic use; D009206:Myocardium / Q000473:pathology*; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D011347:Procollagen / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System / Q000187:drug effects; D013562:Sympathectomy
D047228:Angiotensin II Type 1 Receptor Blockers; D015415:Biomarkers; D010446:Peptide Fragments; D011347:Procollagen; C047202:procollagen Type I N-terminal peptide; D000804:Angiotensin II; D020097:Natriuretic Peptide, Brain; D000450:Aldosterone; D019808:Losartan
Cardiomyopathy; cardiac remodeling; pressure overload; renal sympathetic denervation