Periaortic adipose tissue-specific activation of the renin-angiotensin system contributes to atherosclerosis development in uninephrectomized apoE−/− mice
| Autor: | Hiroyuki Yamada, Noriyuki Wakana, Satoaki Matoba, Yasukiyo Mori, Sou Kishida, Tomomi Ueyama, Daisuke Irie, Hiroaki Matsubara, Koji Ikeda, Hiroki Takata, Hiroyuki Kawahito, Taku Kato, Takehiro Ogata, Yoshiki Akakabe |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Male
medicine.medical_specialty Physiology Angiotensinogen Adipose tissue Aorta Thoracic Disease Biology Nephrectomy Cholesterol Dietary Renin-Angiotensin System Mice Apolipoproteins E Physiology (medical) Internal medicine Renin–angiotensin system Adipocytes medicine Animals Insulin Renal Insufficiency Chronic Risk factor Mice Knockout Apoe mice Angiotensin II Atherosclerosis medicine.disease Mice Inbred C57BL PPAR gamma Disease Models Animal Endocrinology Adipose Tissue Immunology Cardiology and Cardiovascular Medicine Kidney disease |
| Zdroj: | American Journal of Physiology-Heart and Circulatory Physiology. 305:H667-H675 |
| ISSN: | 1522-1539 0363-6135 |
| DOI: | 10.1152/ajpheart.00053.2013 |
| Popis: | Chronic kidney disease (CKD) is an independent risk factor for the development of cardiovascular disease. The perivascular adipose tissue is closely implicated in the development of atherosclerosis; however, the contribution to CKD-associated atherogenesis remains undefined. Eight-week-old apoE-deficient mice were uninephrectomized and fed a high-cholesterol diet starting at 12 wk of age. The atherosclerotic lesion area in the thoracic aorta was comparable in 16-wk-old uninephrectomized (UNX) mice and sham control mice; however, the lesion area was markedly exaggerated in 20-wk-old UNX mice compared with the control (54%, P < 0.05). While the accumulation of monocytes/macrophages and the mRNA expression levels of inflammatory cytokines/chemokines in the thoracic periaortic adipose tissue (PAT) did not differ between the two groups, angiotensinogen (AGT) mRNA expression and the angiotensin II (ANG II) concentration in the PAT were significantly higher in 16-wk-old UNX mice than in the control (1.9- and 1.5-fold increases vs. control, respectively; P < 0.05). ANG II concentrations in both the plasma and epididymal white adipose tissue (WAT) were comparable between the two groups, suggesting that PAT-specific activation of the renin-angiotensin system (RAS) is primarily involved in CKD-associated atherogenesis. The homeostasis model assessment-insulin resistance (HOMA-IR) index and plasma insulin level after glucose loading were significantly elevated in 16-wk-old UNX mice. In vitro stimulation of preadipocytes with insulin exaggerated the AGT mRNA expression along with increased mRNA expression of PPARγ. These findings suggest that PAT-specific RAS activation probably primarily contributes in accelerating atherosclerotic development in UNX mice and could thus represent a therapeutic target for preventing CKD-associated atherogenesis. |
| Databáze: | OpenAIRE |
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