Download the Free Unbound MEDLINE PubMed App to your smartphone or tablet.
Available for iPhone, iPad, iPod touch, and Android.
Circulation research [journal]
- Ali j. Marian: life and science are one. [Journal Article]
- Circ Res 2014 Aug 29; 115(6):549-51.
- Finding the Missing Link Between the Unfolded Protein Response and O-GlcNAcylation in the Heart. [Journal Article]
- Circ Res 2014 Aug 29; 115(6):546-8.
- Gene therapy for hypercholesterolemia: sweet dreams and flying machines. [Editorial]
- Circ Res 2014 Aug 29; 115(6):542-5.
- Lack in Treatment Options for Virus-Induced Inflammatory Cardiomyopathy: Can iPS-Derived Cardiomyocytes Close the Gap? [Editorial]
- Circ Res 2014 Aug 29; 115(6):540-1.
- Extending human induced pluripotent stem cell technology to infectious diseases: new model for viral myocarditis. [Editorial]
- Circ Res 2014 Aug 29; 115(6):537-9.
- FH4=STAP1. Another Gene for Familial Hypercholesterolemia? Relevance to Cascade Testing and Drug Development? [Editorial]
- Circ Res 2014 Aug 29; 115(6):534-6.
- Basigin Mediates Pulmonary Hypertension by Promoting Inflammation and Vascular Smooth Muscle Cell Proliferation. [JOURNAL ARTICLE]
- Circ Res 2014 Aug 22.
Rationale: Cyclophilin A (CyPA) is secreted from vascular smooth muscle cells (VSMCs) by oxidative stress and promotes VSMC proliferation. However, the role of extracellular CyPA and its receptor Basigin (Bsg, encoded by Bsg) in the pathogenesis of pulmonary hypertension (PH) remains to be elucidated. Objective: To determine the role of CyPA/Bsg signaling in the development of PH. Methods and Results: In the pulmonary arteries (PA) of PH patients, immunostaining revealed strong expression of CyPA and Bsg. The PA of CyPA(+/-) and Bsg(+/-) mice exposed to normoxia did not differ in morphology compared with their littermate controls. In contrast, CyPA(+/-)and Bsg(+/-) mice exposed to hypoxia for 4 weeks revealed significantly reduced right ventricular systolic pressure (RVSP), PA remodeling and RV hypertrophy compared with their littermate controls. These features were unaltered by bone marrow reconstitution. To further evaluate the role of vascular Bsg, we harvested pulmonary VSMCs from Bsg(+/+) and Bsg(+/-) mice. Proliferation was significantly reduced in Bsg(+/-) compared with Bsg(+/+) VSMCs. Mechanistic studies demonstrated that Bsg(+/-) VSMCs revealed reduced extracellular signal-regulated kinase (ERK)1/2 activation and less secretion of cytokines/chemokines and growth factors (e.g. PDGF-BB). Finally, in the clinical study, plasma CyPA levels in PH patients were increased in accordance with the severity of pulmonary vascular resistance. Furthermore, event-free curve revealed that high plasma CyPA levels predicted poor outcome in PH patients. Conclusions: These results indicate the crucial role of extracellular CyPA and vascular Bsg in the pathogenesis of PH.
- Safety and Efficacy of Ixmyelocel-T: An Expanded, Autologous Multi-Cellular Therapy, in Dilated Cardiomyopathy. [JOURNAL ARTICLE]
- Circ Res 2014 Aug 20.
Rationale: Ixmyelocel-T is associated with a wide range of biological activities relevant to tissue repair and regeneration. Objective: To evaluate the safety and efficacy of ixmyelocel-T in 2 prospective randomized Phase 2A Trials administered via mini-thoracotomy or intramyocardial catheter injections in patients with dilated cardiomyopathy (DCM) stratified by ischemic or non-ischemic status. Methods and Results: In IMPACT-DCM patients were randomized to either ixmyelocel-T or standard of care control in a 3:1 ratio (n=39) and ixmyelocel-T was administered intramyocardially via mini-thoracotomy. In Catheter-DCM patients were randomized to either ixmyelocel-T or standard of care control in a 2:1 ratio (n=22); ixmyelocel-T was administered intramyocardially using the NOGA® Myostar catheter. Only patients randomized to ixmyelocel-T underwent bone marrow aspiration and injections. In the two studies, a total of 61 patients were randomized, and 59 were treated or received standard of care. Fewer ischemic patients treated with ixmyelocel-T experienced a major adverse cardiovascular event (MACE) during follow up compared to control patients. A similar benefit was not seen in the non-ischemic patients. Heart failure (HF) exacerbation was the most common MACE. Ixmyelocel-T treatment was associated with improved NYHA Class, 6-minute walk distance, and Minnesota Living with Heart Failure Questionnaire scores in the ischemic population relative to control; a similar trend was not observed in the non-ischemic population. Conclusions: Intramyocardial injection with ixmyelocel-T reduces MACE and improves symptoms in patients with ischemic DCM but not non-ischemic DCM.
- A Detailed Analysis of Bone Marrow from Patients with Ischemic Heart Disease and Left Ventricular Dysfunction: BM CD34, CD11b and Clonogenic Capacity as Biomarkers for Clinical Outcomes. [JOURNAL ARTICLE]
- Circ Res 2014 Aug 18.
Rationale: Bone marrow (BM) cell therapy for ischemic heart disease (IHD) has shown mixed results. Before the full potency of BM cell therapy can be realized, it is essential to understand the BM niche following acute myocardial infarction (AMI). Objective: To study the BM composition in patients with IHD and severe left ventricular dysfunction (LVD). Methods and Results: BM from 280 patients with IHD and LVD were analyzed for cell subsets by flow cytometry and colony assays. BM CD34(+) cell percentage was decreased 7 days after AMI (mean of 1.9% vs. 2.3-2.7% in other cohorts; p < 0.05). BM-derived endothelial colonies were significantly decreased (p < 0.05). Increased BM CD11b(+) cells associated with worse left ventricular ejection fraction (LVEF) after AMI (p < 0.05). While increased BM CD34(+) percentage associated with greater improvement in LVEF (+9.9% vs. +2.3%, p=0.03, for AMI patients; and +6.6% vs. -0.02%, p=0.021 for chronic IHD patients), decreased BM CD34(+) percentage in chronic IHD patients correlated with decrement in LVEF after cell therapy (-2.9% vs. +0.7%, p=0.0355). Conclusions: In this study we show a heterogeneous mixture of BM cell subsets, decreased endothelial colony capacity, a CD34(+) cell nadir seven days after AMI, a negative correlation between CD11b percentage and post-infarct LVEF, and positive correlation of CD34 percentage with change in LVEF after cell therapy. These results serve as a possible basis for the small clinical improvement seen in autologous BM cell therapy trials and support selection of potent cell subsets and/or reversal of co-morbid BM impairment.
- Correction. [Journal Article]
- Circ Res 2014 Aug 15; 115(5):e10.