Both pelvic organ prolapse (POP) and osteoporosis are age-related diseases in older aged women. Both POP and bone metabolism may be associated with collagen metabolism. Our study determined the relationship between POP and bone mineral density (BMD) of the lumbar spine and femur neck in postmenopausal women. We selected 554 postmenopausal women (aged 50-79 years) and divided them into two groups (moderate to severe POP and absent to mild POP). We compared the BMDs of the lumbar spine and femur neck between the moderate to severe POP and absent to mild POP groups. Lumbar spine BMD was inversely correlated with POP severity (p = 0.001). However, after adjusting for age, time since menopause, height, weight, body mass index (BMI), and vaginal delivery, the BMDs of both the lumbar spine and femur neck were not significantly different between the moderate to severe POP and absent to mild POP groups (p = 0.583 and p = 0.305, respectively). A lower BMD is associated with increased fracture risk and we postulated that women with severe POP would have an increased risk of osteoporotic fracture.
ID 54365 Poster Board 159 Background and Significance: Heart failure (HF) is characterized by aberrant cardiac beta-adrenergic receptor (b-AR) signaling, leading to upregulation of GPCR kinase 2 (GRK2) and subsequent phosphorylation and desensitization of b-ARs. A peptide inhibitor of GRK2, comprised of the last 194 carboxyl-terminal amino acids of GRK2 (bARKct), has been shown to bind to the G protein beta-gamma subunits, preventing GRK2 binding and b-AR desensitization. Overexpression of bARKct attenuates HF and improves outcomes in animal models. Emerging evidence indicates that following oxidative stress, mitogen-activated protein kinases (MAPKs) phosphorylate the Ser670 (S670) residue of GRK2, which induces GRK2 binding to Hsp90 and localization to mitochondria, where pro-death pathways are initiated. As S670 is also found in bARKct it may prevent endogenous GRK2 accumulation in the mitochondria. We hypothesize that bARKct-mediated cardioprotection in HF is due primarily to mitochondrial GRK2 blockade by bARKct. To test this notion, our lab has generated a cardiac-specific mutant bARKct-S670A transgenic mouse harboring a Ser-to-Ala mutation at the S670 residue that prevents Hsp90 binding and allows for endogenous GRK2 to continue to translocate to the mitochondria upon ischemic injury, while retaining bARKct in the cytosol to act on b-AR signaling pathways.Methods: In vivo hemodynamic analysis was performed to assess cardiac function in bARKct and bARKct-S670A transgenic mice and respective normal littermate controls (NLCs). Additionally, intracellular cyclic AMP (cAMP) levels in AC16 cardiomyocytes transfected with bARKct or bARKCt-S670A, and bARKct-S670D plasmids were quantified in response to increasing doses of isoproterenol.Results: Early hemodynamic analysis of the bARKct-S670A mice has demonstrated increased baseline contractility in bARKct-S670A mice compared to NLC mice, indicating comparable cardioprotective effects to bARKct mice lacking the Ser-to-Ala mutation, which are mediated by canonical pathways. In vitro cAMP quantification revealed AC16s transfected with bARKct, bARKct-S670A, and bARKct-S670D plasmids increased cAMP accumulation in response to increasing doses of isoproterenol compared to control.
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