Back to Search
Start Over
Macrophage depletion protects against endothelial dysfunction and cardiac remodeling in angiotensin II hypertensive mice
- Source :
- Clinical and experimental hypertension (New York, N.Y. : 1993). 43(8)
- Publication Year :
- 2021
-
Abstract
- Objective: Hypertension is associated with a low-grade systemic inflammation in cardiovascular system. Macrophage infiltration may initiate an inflammatory process that contributes to vascular and ventricular remodeling in hypertensive human and mice. The present study investigated the effect of chemical depletion of macrophage using liposome encapsulated clodronate (LEC) on cardiac hypertrophy and remodeling in angiotensin (Ang) II hypertensive mice.Methods: C57BL/6 mice received an Ang II (1.1 mg/kg/day with a minipump) infusion for 2 weeks to induce hypertension. Endothelium-dependent relaxation (ED) was examined by organ bath, hematoxylin and staining and Masson-Trichrome staining were used to evaluate aorta and cardiac hypertrophy and fibrosis.Results: Ang II infusion significantly increased systolic blood pressure (SBP), cardiac hypertrophy and fibrosis, and impaired EDR accompanied by increased macrophage infiltration in the heart. Treatment with LEC significantly lowered Ang II-induced cardiac hypertrophy and fibrosis and cardiac macrophage infiltration, and improved EDR with a mild reduction in SBP. Ang II increased the expression of inflammatory cytokines tumor necross factor alpha and interleukin 1 beta and profibrotic factors transforming growth factor beta 1 and fibronectin in the heart, with was reduced by LEC treatment. Treatment with LEC prevented Ang II-induced the phosphorphorylation of ERK1/2 and c-Jun-N-terminal kinase.Conclusions: Our study suggests that cardiac macrophage may be critical for hypertensive cardiac hypertrophy and remodeling, the underlying mechanisms may involve initial heart inflammation and the activation of hypertrophic MAPKs pathway.
- Subjects :
- medicine.medical_specialty
Physiology
030204 cardiovascular system & hematology
Systemic inflammation
Proinflammatory cytokine
03 medical and health sciences
Mice
0302 clinical medicine
Fibrosis
medicine.artery
Internal medicine
Renin–angiotensin system
Internal Medicine
medicine
Animals
030212 general & internal medicine
Endothelial dysfunction
Ventricular remodeling
Aorta
Ventricular Remodeling
business.industry
Angiotensin II
Macrophages
Myocardium
General Medicine
medicine.disease
Mice, Inbred C57BL
Endocrinology
Hypertension
cardiovascular system
medicine.symptom
business
Subjects
Details
- ISSN :
- 15256006
- Volume :
- 43
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- Clinical and experimental hypertension (New York, N.Y. : 1993)
- Accession number :
- edsair.doi.dedup.....ac56b45eafa2ae40612871f6d2341129