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Rationale: Human studies and mouse models have provided evidence for angiotensin II (Ang II)-based mechanisms as an underlying cause of aneurysms localized to the ascending aorta. In agreement with this associative evidence, we have published recently that Ang II infusion induces aneurysmal pathology in the ascending aorta.Objective: The aim of this study was to define the role of angiotensin II type 1a (AT 1a ) receptors and their cellular location in Ang II-induced ascending aortic aneurysms (AAs). Methods and Results: Male LDL receptor؊/؊ mice were fed a saturated fat-enriched diet for 1 week before osmotic mini-pump implantation and infused with either saline or Ang II (1000 ng/kg per minute) for 28 days. Intimal surface areas of ascending aortas were measured to quantify ascending AAs. Whole body AT 1a receptor deficiency ablated Ang II-induced ascending AAs (P<0.001). To determine the role of AT 1a receptors on leukocytes, LDL receptor ؊/؊ ؋AT 1a receptor ؉/؉ or AT 1a receptor ؊/؊ mice were irradiated and repopulated with bone marrow-derived cells isolated from either AT 1a receptor ؉/؉ or AT 1a receptor ؊/؊ mice. Deficiency of AT 1a receptors in bone marrow-derived cells had no effect on Ang II-induced ascending AAs. To determine the role of AT 1a receptors on vascular wall cells, we developed AT 1a receptor floxed mice with depletion on either smooth muscle or endothelial cells using Cre driven by either SM22 or Tek, respectively. AT 1a receptor deletion in smooth muscle cells had no effect on ascending AAs. In contrast, endothelial-specific depletion attenuated this pathology. Key Words: ascending aneurysm Ⅲ angiotensin II Ⅲ AT 1a receptor Ⅲ Tek-cre A scending aortic aneurysm (AA) is an asymptomatic expansion of this restricted region in which rupture has catastrophic consequences. 1 It has now become apparent that ascending AAs have a significantly higher incidence than originally thought. Furthermore, studies and communities in which autopsies are routinely performed have demonstrated that the incidence of aortic aneurysms is increasing. 2 Recent human and experimental studies have inferred a role for angiotensin II (Ang II) in the development of ascending AAs. [3][4][5][6] Ascending AAs can be generated in transgenic mice that express a common mutation of fibrillin-1 present in patients with Marfan syndrome. There are also several other genes that have been associated with AAs. 4 The aortic dilation that is localized to the ascending region is prevented by the administration of the AT 1 receptor antagonist, losartan. 5 Retrospective analysis of pharmacological treatments given to individuals with Marfan syndrome demonstrated that administration of losartan attenuated dilation of the ascending aorta. 3 Prospective evaluations of angiotensin receptor antagonists are currently being performed in populations afflicted with Marfan syndrome. 7 Ang II has diverse effects that could be implicated in aneurysm formation in the ascending aorta. Ang II exerts its bioactive effects mainly via stimulation o...

The breast cancer-associated T2A10 clone was originally isolated from a cDNA library enriched for tumour messenger ribonucleic acids. Our survey of 125 microarrayed primary tumour tissues using affinity purified polyclonal antibodies has revealed that corresponding protein is overexpressed in invasive breast cancer and is weakly expressed in kidney and prostate tumours. Now known as RNF11, the gene encodes a RING-H2 domain and a PY motif, both of which mediate protein -protein interactions. In particular, the PPPPY sequence of RNF11 PY motif is identical to that of Smad7, which has been shown to bind to WW domains of Smurf2, an E3 ubiquitin ligase that mediates the ubiquitination and degradation of the TGFb receptor complex. Using various mutants of RNF11 in GST pulldown and immunoprecipitation assays, we found that RNF11 interacts with Smurf2 through the PY motif, leading to ubiquitination of both proteins. Smurf2 plays an active role in the repression of TGFb signalling, and our data indicate that overexpression of RNF11, through its interaction with Smurf2, can restore TGFb responsiveness in transfected cells.

Objective: To estimate the prevalence of malnutrition among free-living elderly in a rural population of south India. Design: Cross-sectional study. Nutritional status was assessed using the Mini Nutritional Assessment (MNA) questionnaire, which is an eighteen-item nutritional screening instrument used in the elderly. Setting: Kaniyambadi block, a rural development block in the state of Tamil Nadu, south India. Subjects: Community-dwelling elderly (aged 60 years and above). Results: As evaluated by the MNA, 14 % of the 227 subjects were malnourished and 49 % were at risk of malnourishment. No significant difference was found between men and women. The majority of the elderly were living with their children, had no income and consumed three meals per day. Older age (P , 0?001), decreased food intake (P , 0?001) and consuming fewer meals (P , 0?001) were independently associated with lower MNA scores. Conclusions: More than 60 % of the subjects had low MNA scores (,23?5) indicating that deficient protein-energy intake is common among rural elderly of south India and requires more attention.