Platelet endothelial cell adhesion molecule-1 (PECAM-1, CD31), an adhesion molecule expressed on hematopoietic and endothelial cells, mediates apoptosis, cell proliferation, and migration and maintains endothelial integrity in addition to its roles as a modulator of lymphocyte and platelet signaling and facilitator of neutrophil transmigration. Recent data suggest that CD31 functions as a scaffolding protein to regulate phosphorylation of the signal transducers and activators of transcription (STAT) family of signaling molecules, particularly STAT3 and STAT5. STAT3 regulates the acute phase response to innate immune stimuli such as lipopolysaccharide (LPS) and promotes recovery from LPS-induced septic shock. Here we demonstrate that CD31-deficient mice have reduced survival during endotoxic LPS-induced shock. As compared to wild-type controls, CD31-deficient mice showed enhanced vascular permeability; increased apoptotic cell death in liver, kidney, and spleen; and elevated levels of serum tumor necrosis factor ␣ (TNF-␣), interferon ␥ (IFN␥), MCP-1, MCP-5, sTNRF, and IL-6. In response to LPS in vivo and in vitro, splenocytes and endothelial cells from knockout mice had reduced levels of phosphorylated STAT3. These results suggest that CD31 is necessary for maintenance of endothelial integrity and prevention of apoptosis during septic shock and for STAT3-mediated acute phase responses that promote survival during septic shock. Platelet endothelial cell adhesion molecule-1 (PECAM-1, CD31) belongs to the immunoglobulin family of cell adhesion molecules.

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Gender differences in cardiovascular outcomes were compared in asymptomatic men and women with type 2 diabetes (T2DM) in the Detection of Ischemia in Asymptomatic Diabetics (DIAD) study. Of 1123 participants, 290 men and 271 women were randomised to screening with stress myocardial perfusion imaging (MPI); 311 men and 251 women were randomised to no screening. Follow-up was 4.8±0.9 years for the occurrence of cardiac events (CE; cardiac death or non-fatal myocardial infarction). The frequency of abnormal screening was similar in men (24%) and women (19%), (p=0.2), although women trended to have smaller MPI abnormalities. CE rates were lower in women than men (1.7% vs. 3.8%, p=0.04). No CEs occurred in 17 high-risk (UKPDS risk engine) women, whereas 14 (11.2%) occurred in 125 highrisk men. Asymptomatic women with T2DM have significantly better cardiac outcomes than their male counterparts and represent a subgroup for which screening for coronary artery disease does not appear warranted.

The pathogenesis, clinical course, and treatment of chronic heart failure (HF) are different in elderly women from those of patients recruited in the landmark trials of chronic HF. Patients included in these landmark trials were predominantly men whose age was 10-15 years younger than the average age of patients with chronic HF in the United States. Diastolic dysfunction resulting in impaired left ventricular (LV) filling is the preponderant LV functional alteration that leads to chronic HF in elderly women. Gender differences in the LV remodeling process that accompanies chronic cardiac pressure are likely to be responsible for the preponderance of LV diastolic dysfunction over systolic dysfunction in elderly women. In response to chronic pressure overload, the LV wall becomes thicker in women than in men. Consequently, in response to chronic pressure overload, women are able to normalize LV wall stress and preserve LV systolic function to a greater extent than men. However, impaired LV filling is an undesirable consequence of the greater increase in LV wall thickness in women. Thus, clinical observations and therapeutic guidelines derived from data collected in the landmark trials of chronic HF may not apply to elderly women with chronic HF. In view of the lack of evidence-based information needed to guide the management of elderly women with chronic HF, special attention should be given to include a substantial number of elderly women in future therapeutic trials recruiting patients with chronic HF.