Hypertension (Dallas, Tex. 1979), 2008-09, Vol.52 (3), p.556-562
2008
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Details
- Autor(en) / Beteiligte
- Titel
- Modulation of angiotensin II-mediated hypertension and cardiac remodeling by lectin-like oxidized low-density lipoprotein receptor-1 deletion
- Ist Teil von
- Hypertension (Dallas, Tex. 1979), 2008-09, Vol.52 (3), p.556-562
- Ort / Verlag
- United States
- Erscheinungsjahr
- 2008
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- Angiotensin II via type 1 receptor activation upregulates the expression of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), and LOX-1 activation, in turn, upregulates angiotensin II type 1 receptor expression. We postulated that interruption of this positive feedback loop might attenuate the genesis of angiotensin II-induced hypertension and subsequent cardiac remodeling. To examine this postulate, LOX-1 knockout and wild-type mice were infused with angiotensin II or norepinephrine (control for angiotensin II) for 4 weeks. Angiotensin II-, but not norepinephrine-, induced hypertension was attenuated in LOX-1 knockout mice. Angiotensin II-induced cardiac remodeling was also attenuated in LOX-1 knockout mice. Importantly, angiotensin II type 1 receptor expression was reduced, and the expression and activity of endothelial NO synthase were preserved in the tissues of LOX-1 knockout mice given angiotensin II. Reactive oxygen species generation, nicotinamide-adenine dinucleotide phosphate oxidase expression, and phosphorylation of p38 and p44/42 mitogen-activated protein kinases were also much less pronounced in the LOX-1 knockout mice given angiotensin II. These alterations in biochemical and structural abnormalities were associated with preservation of cardiac hemodynamics in the LOX-1 knockout mice. To confirm that fibroblast function is modulated in the absence of LOX-1, cardiac fibroblasts from wild-type and LOX-1 knockout mice were treated with angiotensin II. Indeed, LOX-1 knockout mice cardiac fibroblasts revealed an attenuated profibrotic response on treatment with angiotensin II. These observations provide strong evidence that LOX-1 is a key modulator of the development of angiotensin II-induced hypertension and subsequent cardiac remodeling.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0194-911XeISSN: 1524-4563DOI: 10.1161/hypertensionaha.108.115287Titel-ID: cdi_proquest_miscellaneous_69455184
- Format
- –
- Schlagworte
- Angiotensin II - pharmacology, Animals, Blood Pressure - drug effects, Cells, Cultured, Fibroblasts - cytology, Fibroblasts - physiology, Gene Deletion, Gene Expression - drug effects, Gene Expression - physiology, Hypertension - metabolism, Hypertension - physiopathology, Mice, Mice, Knockout, Myocardium - cytology, Myocardium - metabolism, Nitric Oxide Synthase Type II - genetics, Nitric Oxide Synthase Type III, Norepinephrine - metabolism, Norepinephrine - pharmacology, Oxidative Stress - drug effects, Oxidative Stress - physiology, Receptor, Angiotensin, Type 1 - genetics, Scavenger Receptors, Class E - genetics, Scavenger Receptors, Class E - metabolism, Vasoconstrictor Agents - pharmacology, Ventricular Remodeling - physiology