An open-label dose escalation study to evaluate the safety of administration of nonviral stromal cell-derived factor-1 plasmid to treat symptomatic ischemic heart failure.
*Plasmids; Aged; Brain/blood; Chemokine CXCL12/*genetics/metabolism; Cohort Studies; Dose-Response Relationship; Drug; Echocardiography; Exercise Tolerance; Female; Follow-Up Studies; Genetic Therapy/*adverse effects/*methods; Heart Failure/metabolism/pathology/*therapy; Humans; Male; Middle Aged; Myocardium/metabolism/pathology; Natriuretic Peptide; Peptide Fragments/blood; Positron-Emission Tomography; Quality of Life; Treatment Outcome
RATIONALE: Preclinical studies indicate that adult stem cells induce tissue repair by activating endogenous stem cells through the stromal cell-derived factor-1:chemokine receptor type 4 axis. JVS-100 is a DNA plasmid encoding human stromal cell-derived factor-1. OBJECTIVE: We tested in a phase 1, open-label, dose-escalation study with 12 months of follow-up in subjects with ischemic cardiomyopathy to see if JVS-100 improves clinical parameters. METHODS AND RESULTS: Seventeen subjects with ischemic cardiomyopathy, New York Heart Association class III heart failure, with an ejection fraction
Penn Marc S; Mendelsohn Farrell O; Schaer Gary L; Sherman Warren; Farr Maryjane; Pastore Joseph; Rouy Didier; Clemens Ruth; Aras Rahul; Losordo Douglas W
Circulation research
2013
2013-03
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1161/CIRCRESAHA.111.300440" target="_blank" rel="noreferrer noopener">10.1161/CIRCRESAHA.111.300440</a>
Salvianolic Acid B Alleviates Heart Failure by Inactivating ERK1/2/GATA4 Signaling Pathway after Pressure Overload in Mice.
Male; Animals; Mice; Phosphorylation/drug effects; Signal Transduction/*drug effects; Rats; Cell Line; Proto-Oncogene Proteins c-akt/metabolism; Benzofurans/chemistry/*pharmacology; Blood Pressure/drug effects; GATA4 Transcription Factor/metabolism; Heart Failure/metabolism/*pathology; Heart Ventricles/diagnostic imaging; Mitogen-Activated Protein Kinase 1/metabolism; Mitogen-Activated Protein Kinase 3/metabolism; Myocardium/metabolism/pathology; Drugs; Inbred C57BL; Animal; Disease Models; Myocytes; Aorta; Brain/blood; Natriuretic Peptide; Cardiac/cytology/drug effects/metabolism; Chinese Herbal/chemistry/pharmacology; Thoracic/surgery
BACKGROUND: Heart failure(HF) is a dangerous disease that affects millions of patients. Radix Salvia is widely used in Chinese clinics to treat heart diseases. Salvianolic acid B(SalB) is the major active component of Radix Salvia. This study investigated the mechanisms of action and effects of SalB on HF in an experimental mouse model of HF. METHODS: We created a mouse model of HF by inducing pressure overload with transverse aortic constriction(TAC) surgery for 2 weeks and compared among 4 study groups: SHAM group (n = 10), TAC group (n = 9), TAC+MET group (metprolol, positive drug treatment, n = 9) and TAC+SalB group (SalB, 240 mg*kg-1*day-1, n = 9). Echocardiography was used to evaluate the dynamic changes in cardiac structure and function in vivo. Plasma brain natriuretic peptide (BNP) concentration was detected by Elisa method. In addition, H9C2 rat cardiomyocytes were cultured and Western blot were implemented to evaluate the phosphorylation of ERK1/2, AKT, and protein expression of GATA4. RESULTS: SalB significantly inhibited the phosphorylation of Thr202/Tyr204 sites of ERK1/2, but not Ser473 site of AKT, subsequently inhibited protein expression of GATA4 and plasma BNP(P \textless 0.001), and then inhibited HF at 2 weeks after TAC surgery. CONCLUSIONS: Our data provide a mechanism of inactivating the ERK1/2/GATA4 signaling pathway for SalB inhibition of the TAC-induced HF.
Yu Juan; Chen Renshan; Tan Yafang; Wu Jiashin; Qi Jianyong; Zhang Minzhou; Gu Weiwang
PloS one
2016
2016
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1371/journal.pone.0166560" target="_blank" rel="noreferrer noopener">10.1371/journal.pone.0166560</a>
The cardiomyopathy of iron deficiency.
Adult; Female; Humans; Echocardiography; Electrocardiography; Hematocrit; Cardiac Output; Anemia; Ventricular Dysfunction; Transesophageal; Brain/blood; Natriuretic Peptide; Iron-Deficiency/blood/*complications/physiopathology; Left/blood/diagnostic imaging/*etiology; Low/etiology
Iron-deficiency anemia can have deleterious effects on the heart. Herein, we describe the effects of iron deficiency on the heart as corroborated with electrocardiography, radiology, echocardiography, and cardiac catheterization. We review the pathophysiology, clinical features, and management of iron-deficiency-induced cardiomyopathy.
Hegde Nikita; Rich Michael W; Gayomali Charina
Texas Heart Institute journal
2006
1905-6
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).