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Xing D.,Vascular Biology and Hypertension Program | Kapadia A.,University of Alabama at Birmingham | Chen Y.-F.,Vascular Biology and Hypertension Program | Oparil S.,Vascular Biology and Hypertension Program | And 2 more authors.
Arteriosclerosis, Thrombosis, and Vascular Biology | Year: 2014

OBJECTIVE - 17β-Estradiol (E2) offers cardiovascular protection in young female animals and postmenopausal women. In contrast, randomized trials of menopausal hormones performed in older women have shown harm or no cardiovascular benefit. We hypothesize that E2 effects on vascular inflammation are age dependent. APPROACH AND RESULTS - Young (10 weeks) and aged (52 weeks) female C57BL/6 mice were used as source for primary cultures of bone marrow-derived macrophages (BMMs) and vascular smooth muscle cells (VSMCs). E2 pretreatment of cells derived from young mice attenuated C-reactive protein (CRP)-induced expression of inflammatory mediators. In contrast, E2 pretreatment of cells from aged mice did not alter (BMMs) or paradoxically exaggerated (VSMCs) inflammatory mediator response to CRP. Using E2 receptor (ER) knockout mice, we demonstrated that E2 regulates inflammatory response to CRP in BMMs via ERα and in VSMCs via ERβ. BMMs derived from aged (versus young) mice expressed significantly less ERα mRNA and protein. A selective ligand of the novel ER GPR30 reproduced the E2 effects in BMMs and VSMCs. Unlike in young mice, E2 did not reduce neointima formation in ligated carotid arteries of aged CRP transgenic mice. CONCLUSIONS - E2 attenuates inflammatory response to CRP in BMMs and VSMCs derived from young but not aged mice and reduces neointima formation in injured carotid arteries of young but not aged CRP transgenic mice. ERα expression in BMMs is greatly diminished with aging. These data suggest that vasoprotective effects of E2 are age dependent and may explain the vasotoxic effects of E2 seen in clinical trials of postmenopausal women. © 2014 American Heart Association, Inc.


Britton T.,Birmingham Veterans Administration Medical Center | Robinson N.,Memorial Health University Medical Center
Journal of Nuclear Medicine Technology | Year: 2016

18F-FDG PET imaging of tumors has pitfalls and pearls of wisdom that begin at the point of scheduling and continue through the patient interview, the resting phase, the scan itself, and the image review. Interviewing the patient at the time of scheduling, followed by placing a reminder phone call shortly before the appointment, can save a nuclear medicine department the financial loss of wasted doses and missed appointment slots in the schedule. The pitfalls and pearls of wisdom in tumor imaging are ever changing, and the technologist is in a constant state of inquiry about the patient's disease process and ability to comply. Consideration of each item on the worksheets in this article affects every scan. On completing this article, the reader will be able to identify questions that should be asked in the scheduling and preinjection patient interviews, interpret the answers to those questions, determine how the images may be affected, and adapt the scan. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.


Ghimire G.,University of Alabama at Birmingham | Hage F.G.,University of Alabama at Birmingham | Hage F.G.,Birmingham Veterans Administration Medical Center | Heo J.,University of Alabama at Birmingham | Iskandrian A.E.,University of Alabama at Birmingham
Journal of Nuclear Cardiology | Year: 2013

Since its approval by the Food and Drug Administration in 2008, regadenoson has become the most commonly used vasodilator in the United States. Previous reviews have summarized the pre-clinical and clinical data on the use of regadenoson for myocardial perfusion imaging (MPI). Since then, data have emerged on the safety of this agent in special groups of patients such as those with chronic kidney disease, airway disease (asthma and chronic obstructive pulmonary disease), and liver disease. There has also been recent interest in the use of regadenoson in hybrid protocols with exercise as a way to improve patient tolerance and image quality. Finally, although regadenoson was approved for clinical use based on the agreement rate of regadenoson MPI and adenosine MPI with regards to perfusion abnormalities, data are now available on the prognostic data derived from regadenoson MPI. We will briefly summarize these recent reports here in a focused update on the use of regadenoson for MPI. © 2012 American Society of Nuclear Cardiology.


Yang S.,University of Alabama at Birmingham | Abraham E.,University of Alabama at Birmingham | Agarwal A.,Birmingham Veterans Administration Medical Center | Liu G.,University of Alabama at Birmingham
American Journal of Physiology - Renal Physiology | Year: 2011

Renal fibrosis is a final stage of many forms of kidney disease and leads to impairment of kidney function. The molecular pathogenesis of renal fibrosis is currently not well-understood. microRNAs (miRNAs) are important players in initiation and progression of many pathologic processes including diabetes, cancer, and cardiovascular disease. However, the role of miRNAs in kidney injury and repair is not well-characterized. In the present study, we found a unique miRNA signature associated with unilateral ureteral obstruction (UUO)-induced renal fibrosis. We found altered expression in UUO kidneys of miRNAs that have been shown to be responsive to stimulation by transforming growth factor (TGF)-β1 or TNF-α. Among these miRNAs, miR-21 demonstrated the greatest increase in UUO kidneys. The enhanced expression of miR-21 was located mainly in distal tubular epithelial cells. miR-21 expression was upregulated in response to treatment with TGF-β1 or TNF-α in human renal tubular epithelial cells in vitro. Furthermore, we found that blocking miR-21 in vivo attenuated UUO-induced renal fibrosis, presumably through diminishing the expression of profibrotic proteins and reducing infiltration of inflammatory macrophages in UUO kidneys. Our data suggest that targeting specific miRNAs could be a novel therapeutic approach to treat renal fibrosis. © 2011 the American Physiological Society.


Hage F.G.,University of Alabama at Birmingham | Hage F.G.,Birmingham Veterans Administration Medical Center | Oparil S.,University of Alabama at Birmingham
Current Opinion in Cardiology | Year: 2013

PURPOSE OF REVIEW: Observational studies have shown benefit of hormone therapy, particularly estrogen, in women who begin treatment in the perimenopausal/early postmenopausal period, whereas randomized controlled trials of such therapy in older postmenopausal women have reported harm. These apparently paradoxical findings have led to the 'timing hypothesis' which proposes that estrogen signaling is altered in older women, converting vasoprotective to vasotoxic effects. We reviewed recent literature on age-dependent effects of hormones (particularly estrogen) on the vasculature of women and the fundamental cellular/molecular mechanisms responsible for those effects. RECENT FINDINGS: Observational studies have shown that early menopause is associated with adverse cardiovascular disease outcomes and that starting hormone therapy in the perimenopausal period reduces these outcomes. Mechanistic studies have shown that estrogen modulates injury-induced inflammation, growth factor expression, and oxidative stress in arteries and vascular smooth muscle cells isolated from young women but that these vasoprotective mechanisms are lost in women who are aged and/or deprived of estrogen for prolonged periods of time. SUMMARY: The vasoprotective effects of estrogen are age-dependent and disappear with aging and/or estrogen deprivation. Future studies designed to preserve the vasoprotective effects of estrogen in older women are needed and may lead to innovative approaches to improving women's cardiovascular health. © 2013 Wolters Kluwer Health | Lippincott Williams &Wilkins.

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