Notch activation mediates angiotensin II-induced vascular remodeling by promoting the proliferation and migration of vascular smooth muscle cells.

Notch signaling is involved in an intercellular communication mechanism that is essential for coordinated cell fate determination and tissue morphogenesis. The biological effects of Notch signaling are context-dependent. We investigated the functional and hierarchical relationship between angiotensin (Ang) II receptor signaling and Notch signaling in vascular smooth muscle cells (VSMCs).

Agonist-independent constitutive activity of angiotensin II receptor promotes cardiac remodeling in mice.

The angiotensin II (Ang II) type 1 (AT(1)) receptor mainly mediates the physiological and pathological actions of Ang II, but recent studies have suggested that AT(1) receptor inherently shows spontaneous constitutive activity even in the absence of Ang II in culture cells. To elucidate the role of Ang II-independent AT(1) receptor activation in the pathogenesis of cardiac remodeling, we generated transgenic mice overexpressing AT(1) receptor under the control of α-myosin heavy chain promoter in angiotensinogen-knockout background (AT(1)Tg-AgtKO mice). In AT(1)Tg-AgtKO hearts, redistributions of the Gα(q11) subunit into cytosol and phosphorylation of extracellular signal-regulated kinases were significantly increased, compared with angiotensinogen-knockout mice hearts, suggesting that the AT(1) receptor is constitutively activated independent of Ang II.

Angiotensin II type 1 receptor signaling regulates feeding behavior through anorexigenic corticotropin-releasing hormone in hypothalamus.

The activation of renin-angiotensin system contributes to the development of metabolic syndrome and diabetes as well as hypertension. However, it remains undetermined how renin-angiotensin system is implicated in feeding behavior. Here, we show that angiotensin II type 1 (AT(1)) receptor signaling regulates the hypothalamic neurocircuit that is involved in the control of food intake.

Interaction of myocardial insulin receptor and IGF receptor signaling in exercise-induced cardiac hypertrophy.

Insulin-like growth factor-1 (IGF-1) signaling has recently been implicated in the development of cardiac hypertrophy after long-term endurance training, via mechanisms that may involve energetic stress. Given the potential overlap of insulin and IGF-1 signaling we sought to determine if both signaling pathways could contribute to exercise-induced cardiac hypertrophy following shorter-term exercise training. Studies were performed in mice with cardiac-specific IGF-1 receptor (IGF1R) knockout (CIGFRKO), mice with cardiac-specific insulin receptor (IR) knockout (CIRKO), CIGFRKO mice that lacked one IR allele in cardiomyocytes (IGFR-/-IR+/-), and CIRKO mice that lacked one IGF1R allele in cardiomyocytes (IGFR+/-IR-/-).