Recruitment of macrophages from the spleen contributes to myocardial fibrosis and hypertension induced by angiotensin II

Autor: Ning-Ping Wang, Garret Duron, Wei-Wei Zhang, Zhi-Qing Zhao, Julian L Gendreau, Li-Hui Zhang, James Erskine, Rong-Hua Zheng
Rok vydání: 2017
Předmět:
collagen
Male
0301 basic medicine
Medicine (General)
Cardiac fibrosis
Aorta
Thoracic
Blood Pressure
Smad Proteins
030204 cardiovascular system & hematology
Monocytes
Rats
Sprague-Dawley
0302 clinical medicine
Endocrinology
Fibrosis
Phosphorylation
Myofibroblasts
Chemokine CCL2
Angiotensin II
medicine.anatomical_structure
Cardiology
Original Article
medicine.drug
medicine.medical_specialty
hypertension
Nitric Oxide Synthase Type III
splenectomy
Receptor
Angiotensin
Type 1
Transforming Growth Factor beta1
03 medical and health sciences
R5-920
Internal medicine
Renin–angiotensin system
Internal Medicine
medicine
Animals
Cell Proliferation
Angiotensin II receptor type 1
business.industry
Macrophages
Myocardium
Monocyte
medicine.disease
Angiotensin II AT1 receptor
030104 developmental biology
myocardial fibrosis
Myocardial fibrosis
Telmisartan
business
Spleen
Zdroj: Journal of the Renin-Angiotensin-Aldosterone System: JRAAS
Journal of the Renin-Angiotensin-Aldosterone System, Vol 18 (2017)
ISSN: 1752-8976
1470-3203
DOI: 10.1177/1470320317706653
Popis: Introduction:The purpose of this study was to determine whether macrophages migrated from the spleen are associated with angiotensin II-induced cardiac fibrosis and hypertension.Methods:Sprague-Dawley rats were subjected to angiotensin II infusion in vehicle (500 ng/kg/min) for up to four weeks. In splenectomy, the spleen was removed before angiotensin II infusion. In the angiotensin II AT1 receptor blockade, telmisartan was administered by gastric gavage (10 mg/kg/day) during angiotensin II infusion. The heart and aorta were isolated for Western blot analysis and immunohistochemistry.Results:Angiotensin II infusion caused a significant reduction in the number of monocytes in the spleen through the AT1 receptor-activated monocyte chemoattractant protein-1. Comparison of angiotensin II infusion, splenectomy and telmisartan comparatively reduced the recruitment of macrophages into the heart. Associated with this change, transforming growth factor β1 expression and myofibroblast proliferation were inhibited, and Smad2/3 and collagen I/III were downregulated. Furthermore, interstitial/perivascular fibrosis was attenuated. These modifications occurred in coincidence with reduced blood pressure. At week 4, invasion of macrophages and myofibroblasts in the thoracic aorta was attenuated and expression of endothelial nitric oxide synthase was upregulated, along with a reduction in aortic fibrosis.Conclusions:These results suggest that macrophages when recruited into the heart and aorta from the spleen potentially contribute to angiotensin II-induced cardiac fibrosis and hypertension.
Databáze: OpenAIRE
Externí odkaz: