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  • 1
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    Mitochondrial integrity in a neonatal bovine model of right ventricular dysfunction (2015)
    The American Physiological Society (APS)
    Details
    Publication Date: 2015-01-16
    Description: Right ventricular (RV) function is a key determinant of survival in patients with both RV and left ventricular (LV) failure, yet the mechanisms of RV failure are poorly understood. Recent studies suggest cardiac metabolism is altered in RV failure in pulmonary hypertension (PH). Accordingly, we assessed mitochondrial content, dynamics, and function in hearts from neonatal calves exposed to hypobaric hypoxia (HH). This model develops severe PH with concomitant RV hypertrophy, dilation, and dysfunction. After 2 wk of HH, pieces of RV and LV were obtained along with samples from age-matched controls. Comparison with control assesses the effect of hypoxia, whereas comparison between the LV and RV in HH assesses the additional impact of RV overload. Mitochondrial DNA was unchanged in HH, as was mitochondrial content as assessed by electron microscopy. Immunoblotting for electron transport chain subunits revealed a small increase in mitochondrial content in HH in both ventricles. Mitochondrial dynamics were largely unchanged. Activity of individual respiratory chain complexes was reduced (complex I) or unchanged (complex V) in HH. Key enzymes in the glycolysis pathway were upregulated in both HH ventricles, alongside upregulation of hypoxia-inducible factor-1α protein. Importantly, none of the changes in expression or activity were different between ventricles, suggesting the changes are in response to HH and not RV overload. Upregulation of glycolytic modulators without chamber-specific mitochondrial dysfunction suggests that mitochondrial capacity and activity are maintained at the onset of PH, and the early RV dysfunction in this model results from mechanisms independent of the mitochondria.
    Print ISSN: 1040-0605
    Electronic ISSN: 1522-1504
    Topics: Medicine
    Published by The American Physiological Society (APS)
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  • 2
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    History of Hollenhorst Plaques [Stroke History] (2015)
    American Heart Association (AHA)
    In: Stroke
    Details
    Publication Date: 2015-03-24
    Keywords: Cerebrovascular disease/stroke, Risk Factors, Embolic stroke
    Print ISSN: 0039-2499
    Electronic ISSN: 1524-4628
    Topics: Medicine
    Published by American Heart Association (AHA)
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  • 3
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    TMPRSS2:ERG blocks neuroendocrine and luminal cell differentiation to maintain prostate cancer proliferation (2015)
    Nature Publishing Group (NPG)
    In: Oncogene
    Details
    Publication Date: 2015-07-17
    Description: TMPRSS2:ERG blocks neuroendocrine and luminal cell differentiation to maintain prostate cancer proliferation Oncogene 34, 3815 (July 2015). doi:10.1038/onc.2014.308 Authors: Z Mounir, F Lin, V G Lin, J M Korn, Y Yu, R Valdez, O H Aina, G Buchwalter, A B Jaffe, M Korpal, P Zhu, M Brown, R D Cardiff, J L Rocnik, Y Yang & R Pagliarini
    Print ISSN: 0950-9232
    Topics: Medicine
    Published by Nature Publishing Group (NPG)
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  • 4
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    Guidelines for the Management of Patients With Unruptured Intracranial Aneurysms: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association [AHA/ASA Guideline] (2015)
    American Heart Association (AHA)
    In: Stroke
    Details
    Publication Date: 2015-07-28
    Description: Purpose— The aim of this updated statement is to provide comprehensive and evidence-based recommendations for management of patients with unruptured intracranial aneurysms. Methods— Writing group members used systematic literature reviews from January 1977 up to June 2014. They also reviewed contemporary published evidence-based guidelines, personal files, and published expert opinion to summarize existing evidence, indicate gaps in current knowledge, and when appropriate, formulated recommendations using standard American Heart Association criteria. The guideline underwent extensive peer review, including review by the Stroke Council Leadership and Stroke Scientific Statement Oversight Committees, before consideration and approval by the American Heart Association Science Advisory and Coordinating Committee. Results— Evidence-based guidelines are presented for the care of patients presenting with unruptured intracranial aneurysms. The guidelines address presentation, natural history, epidemiology, risk factors, screening, diagnosis, imaging and outcomes from surgical and endovascular treatment.
    Keywords: AHA Statements and Guidelines
    Print ISSN: 0039-2499
    Electronic ISSN: 1524-4628
    Topics: Medicine
    Published by American Heart Association (AHA)
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  • 5
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    Differential Sex Response to Aspirin in Decreasing Aneurysm Rupture in Humans and Mice [Cerebral Aneurysm] (2016)
    American Heart Association (AHA)
    Details
    Publication Date: 2016-07-14
    Description: We previously found that aspirin decreases the risk of cerebral aneurysm rupture in humans. We aim to assess whether a sex differential exists in the response of human cerebral aneurysms to aspirin and confirm these observations in a mouse model of cerebral aneurysm. A nested case–control analysis from the International Study of Unruptured Intracranial Aneurysms was performed to assess whether a sex differential exists in the response of human cerebral aneurysms to aspirin. A series of experiments were subsequently performed in a mouse model of cerebral aneurysms. Aneurysms were induced with hypertension and elastase injection into mice basal cisterns. We found that aspirin decreased the risk of aneurysm rupture more significantly in men than in women in the International Study of Unruptured Intracranial Aneurysms. In mice, aspirin and cyclooxygenase-2 inhibitor did not affect cerebral aneurysm formation but significantly decreased the incidence of rupture. The incidence of rupture was significantly lower in male versus female mice on aspirin. Gene expression analysis from cerebral arteries showed higher 15-hydroxyprostaglandin dehydrogenase levels in male mice. The rate of cerebral aneurysm rupture was similar in male mice receiving aspirin and 15-hydroxyprostaglandin dehydrogenase inhibitor compared with females receiving aspirin and 15-hydroxyprostaglandin dehydrogenase agonist, signaling a reversal of the sex-differential response to aspirin. Aspirin decreases aneurysm rupture in human and mice, in part through cyclooxygenase-2 pathways. Evidence from animal and human studies suggests a consistent differential effect by sex. 15-Hydroxyprostaglandin dehydrogenase activation in females reduces the incidence of rupture and eliminates the sex-differential response to aspirin.
    Keywords: Cerebral Aneurysm
    Print ISSN: 0194-911X
    Topics: Medicine
    Published by American Heart Association (AHA)
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  • 6
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    No Decline in the Risk of Stroke Following Incident Atrial Fibrillation Since 2000 in the Community: A Concerning Trend [Epidemiology] (2016)
    American Heart Association (AHA)
    Details
    Publication Date: 2016-06-30
    Description: Background While atrial fibrillation is a recognized risk factor for stroke, contemporary data on trends in stroke incidence after the diagnosis of atrial fibrillation are scarce. Methods and Results Olmsted County, MN residents with incident atrial fibrillation or atrial flutter (collectively referred to as AF) from 2000 to 2010 were identified. Cox regression determined associations of year of AF diagnosis with ischemic stroke and transient ischemic attack (TIA) occurring through 2013. Among 3247 AF patients, 321 (10%) had an ischemic stroke/TIA over a mean of 4.6 years (incidence rate [95% CI] per 100 person-years: 2.14 [1.91–2.38]). Two hundred thirty-nine (7%) of 3265 AF patients experienced an ischemic stroke (incidence rate: 1.54 [1.35–1.75]). The risk of both outcomes remained unchanged over time after adjusting for demographics and comorbidities (hazard ratio [95% CI] per year of AF diagnosis: 1.00 [0.96–1.04] for ischemic stroke/TIA; 1.01 [0.96–1.06] for ischemic stroke only). In analyses restricted to patients with prescription information, the rates of anticoagulation use did not change over time, reaching 50.8% at 1 year after AF diagnosis. Further adjustment for anticoagulation use did not alter the temporal trends in stroke incidence (hazard ratio [95% CI] per year of AF diagnosis: 1.06 [0.97–1.15] for ischemic stroke/TIA; 1.08 [0.98–1.20] for ischemic stroke only). Conclusions Strokes/TIAs are frequent after AF, occurring in 10% of patients after 5 years of follow-up. The occurrence of stroke/TIA did not decline over the last decade, which may be influenced by a leveling off of anticoagulation use. This concerning trend has major public health implications.
    Keywords: Atrial Fibrillation, Epidemiology, Ischemic Stroke, Transient Ischemic Attack (TIA)
    Electronic ISSN: 2047-9980
    Topics: Medicine
    Published by American Heart Association (AHA)
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  • 7
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    Tubuloglomerular feedback responses in offspring of dexamethasone-treated ewes (2017)
    The American Physiological Society (APS)
    Details
    Publication Date: 2017-10-04
    Description: Via developmental programming, prenatal perturbations, such as exposure to glucocorticoids and maternal malnutrition alter kidney development and contribute to the development of hypertension. To examine the possibility that alterations in tubuloglomerular feedback (TGF) contribute to the development of hypertension in offspring following maternal dexamethasone treatment (Dex) in early gestation, studies were conducted in fetal sheep and lambs. Pregnant ewes were infused with dexamethasone (0.48 mg/h) at 26–28 days gestation. No differences were observed in mean arterial pressure, glomerular filtration rate. or electrolyte excretion rates between the Dex and Untreated fetuses or lambs. Gestational exposure to Dex markedly enhanced TGF sensitivity, as the turning point in Dex-treated fetuses was significantly lower (12.9 ± 0.9 nl/min; P 〈 0.05) compared with Untreated fetuses (17.0 ± 1.0 nl/min). This resetting of TGF sensitivity persisted after birth ( P 〈 0.01). TGF reactivity did not differ between the groups in fetuses or lambs. In response to nitric oxide inhibition, TGF sensitivity increased (the turning point decreased) and reactivity increased in Untreated fetuses and lambs, but these effects were blunted in the Dex-treated fetuses and lambs. Our data suggest that an altered TGF response may be an underlying renal mechanism contributing to the development of hypertension in the Dex model of fetal programming. The lower tonic level of NO production in these dexamethasone-exposed offspring may contribute to the development of hypertension as adults.
    Print ISSN: 1931-857X
    Electronic ISSN: 1522-1466
    Topics: Medicine
    Published by The American Physiological Society (APS)
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