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Macrophage Depletion Improves Endothelial Insulin Resistance and Protects against Cardiovascular Injury in Salt-Sensitive Hypertension
- Source :
- BioMed Research International, Vol 2020 (2020), BioMed Research International
- Publication Year :
- 2020
- Publisher :
- Hindawi, 2020.
-
Abstract
- Vascular endothelial insulin signaling is critical for the maintenance of vascular and metabolic homeostasis. We have previously shown that in hypertensive Dahl rats, impaired vascular insulin action is linked to angiotensin II activation of the NFκB inflammatory pathway. Macrophage polarization (M1) has implicated in hypertensive and metabolic diseases. Here, we investigated the effect of macrophage depletion using liposome-encapsulated clodronate (LEC) on endothelial insulin resistance and cardiovascular remodeling in Dahl salt-sensitive (DS) rats. High salt intake (HS) for 5 weeks increased systolic blood pressure (SBP: 192±5 vs. 144±4 mmHg in NS, p<0.05), aortic and cardiac hypertrophy, cardiac fibrosis, and impaired acetylcholine- and insulin-induced vasorelaxation, accompanied by impaired insulin activation of endothelial nitric oxide synthases (eNOS)/NO signaling. HS rats had a significant increase in CD68 (a monocyte/macrophage marker) expression in the aorta and the heart. LEC reduced SBP (168±5 mmHg, p<0.05) and cardiovascular injury and improved acetylcholine- and insulin-mediated vasorelaxation and insulin signaling molecules with a reduction in the macrophage infiltration in the aorta and the heart. HS rats also manifested an increase in the aortic expressions of inflammatory cytokines, including the ratio of phosphorylated inhibitory kappa B (Iκb)/Iκb, tumor necrosis factor α, and phosphorylated c-Jun N-terminal kinase (JNK) and oxidative stress, which were reduced in HS/LEC rats. Our results suggest that in salt-sensitive hypertension, macrophage may importantly contribute to endothelial insulin resistance, vascular inflammation, and injury. These findings support the idea that macrophages may be a new target for immunotherapy of vasculopathy in hypertensive and metabolic disorders.
- Subjects :
- 0301 basic medicine
medicine.medical_specialty
Article Subject
Cardiac fibrosis
medicine.medical_treatment
Cardiovascular Abnormalities
Macrophage polarization
030204 cardiovascular system & hematology
Sodium Chloride
General Biochemistry, Genetics and Molecular Biology
Proinflammatory cytokine
03 medical and health sciences
0302 clinical medicine
Insulin resistance
Internal medicine
medicine
Animals
Humans
Sodium Chloride, Dietary
General Immunology and Microbiology
biology
business.industry
Insulin
Angiotensin II
Macrophages
Endothelial Cells
General Medicine
medicine.disease
Rats
Insulin receptor
Disease Models, Animal
030104 developmental biology
Endocrinology
Hypertension
biology.protein
Medicine
Tumor necrosis factor alpha
Insulin Resistance
business
Research Article
Subjects
Details
- Language :
- English
- ISSN :
- 23146133
- Database :
- OpenAIRE
- Journal :
- BioMed Research International
- Accession number :
- edsair.doi.dedup.....cc41fe55b0d62c4684a8f50ed4ea5908
- Full Text :
- https://doi.org/10.1155/2020/5073762