Asian Science Citation Index is committed to provide an authoritative, trusted and significant information by the coverage of the most important and influential journals to meet the needs of the global scientific community.  
ASCI Database
308-Lasani Town,
Sargodha Road,
Faisalabad, Pakistan
Fax: +92-41-8815544
Contact Via Web
Suggest a Journal
Articles by T. P. Cappola
Total Records ( 4 ) for T. P. Cappola
  B Ky , S. E Kimmel , R. N Safa , M. E Putt , N. K Sweitzer , J. C Fang , D. B Sawyer and T. P. Cappola

Background— Neuregulin-1 (NRG-1) is a paracrine factor released by microvascular endothelial cells that has cardioprotective effects in animal models of heart failure. However, circulating NRG-1 has not been studied in human heart disease. We used a novel immunoassay to test whether circulating NRG-1β is associated with disease severity and clinical outcomes in chronic heart failure.

Methods and Results— Serum NRG-1β was quantified in 899 outpatients in the Penn Heart Failure Study, a referral cohort representing a broad spectrum of systolic heart failure. Circulating NRG-1β was significantly elevated in patients with worse disease severity (median, 6.2 ng/mL for New York Heart Association class IV versus 4.4 ng/mL for class I; P=0.002). In adjusted models, NRG-1β was independently associated with an increased risk of death or cardiac transplantation over a median follow-up of 2.4 years (adjusted hazard ratio, 1.58; 95% confidence interval, 1.04 to 2.39; P=0.03 comparing fourth versus first NRG-1β quartile). Associations with outcome differed by heart failure cause and symptom severity, with the strongest associations observed in patients with ischemic cardiomyopathy (interaction P=0.008) and New York Heart Association class III/IV symptoms (interaction P=0.01). These findings were all independent of brain natriuretic peptide, and assessment of NRG-1β and brain natriuretic peptide jointly provided better risk stratification than each biomarker individually in patients with ischemic or New York Heart Association class III/IV heart failure.

Conclusions— Circulating NRG-1β is independently associated with heart failure severity and risk of death or cardiac transplantation. These findings support a role for NRG-1/ErbB signaling in human heart failure and identify serum NRG-1β as a novel biomarker that may have clinical applications.

  M. E Putt , S Hannenhalli , Y Lu , P Haines , H. R Chandrupatla , E. E Morrisey , K. B Margulies and T. P. Cappola

Background— Pathological stresses induce heart failure in animal models through activation of multiple cardiac transcription factors (TFs) working cooperatively. However, interactions among TFs in human heart failure are less understood. Here, we use genomic data to examine the evidence that 5 candidate TF families coregulate gene expression in human heart failure.

Methods and Results— RNA isolates from failing (n=86) and nonfailing (n=16) human hearts were hybridized with Affymetrix HU133A arrays. For each gene on the array, we determined conserved MEF2, NFAT, NKX , GATA , and FOX binding motifs within the –1-kb promoter region using human-murine sequence alignments and the TRANSFAC database. Across 9076 genes expressed in the heart, TF-binding motifs tended to cluster together in nonrandom patterns within promoters of specific genes (P values ranging from 10–2 to 10–21), suggesting coregulation. We then modeled differential expression as a function of TF combinations present in promoter regions. Several combinations predicted increased odds of differential expression in the failing heart, with the highest odds ratios noted for genes containing both MEF2 and NFAT binding motifs together in the same promoter region (peak odds ratio, 3.47; P=0.005).

Conclusions— These findings provide genomic evidence for coregulation of myocardial gene expression by MEF2 and NFAT in human heart failure. In doing so, they extend the paradigm of combinatorial regulation of gene expression to the human heart and identify new target genes for mechanistic study. More broadly, we demonstrate how integrating diverse sources of genomic data yields novel insight into human cardiovascular disorders.

  D. L Dries , B Ky , A. H.B Wu , J. E Rame , M. E Putt and T. P. Cappola

Background— B-type natriuretic peptide (BNP) is produced as a biologically inactive prohormone (proBNP1-108), processed, and released as an inactive amino acid N-terminal fragment (proBNP1-76) and a biologically active carboxyl-terminal fragment (proBNP77-108 or BNP32). We hypothesized that simultaneous assessment of proBNP1-108 and active BNP32, as an index of natriuretic peptide processing efficiency, would improve risk stratification in patients with chronic systolic heart failure.

Methods and Results— We quantified plasma proBNP1-108 and BNP32 in 756 participants in the Penn Heart Failure Study, a prospective cohort of outpatients with predominantly systolic heart failure. Cox models were used to determine the association between biomarker level at the time of study entry and incident risk of adverse cardiovascular outcomes. A significant amount of unprocessed proBNP1-108 circulates in patients with systolic heart failure (median, 271 pg/mL; interquartile range, 65 to 825). Higher levels of proBNP1-108 were associated with an increased risk of all-cause death or cardiac transplantation (adjusted hazard ratio, 4.9; 95% CI, 2.5 to 9.7; P<0.001, comparing third versus first proBNP1-108 tertile). ProBNP1-108 provided additive information to BNP32 risk assessment, particularly in patients with BNP32 less than the median of 125 pg/mL (adjusted hazard ratio, 1.4; 95% CI, 1.2 to 1.8; P<0.001 per doubling of proBNP1-108).

Conclusions— Circulating proBNP1-108 is independently associated with an increased risk of adverse cardiovascular outcomes in ambulatory patients with chronic systolic heart failure. The combined assessment of BNP32 and proBNP1-108 provides additional information in determining risk of adverse clinical outcomes, particularly in patients with low BNP32 values that might otherwise be reassuring to the clinician.

Copyright   |   Desclaimer   |    Privacy Policy   |   Browsers   |   Accessibility