PMID- 18262563
OWN - NLM
STAT- MEDLINE
DCOM- 20080417
LR  - 20151119
IS  - 0022-4804 (Print)
IS  - 0022-4804 (Linking)
VI  - 145
IP  - 2
DP  - 2008 Apr
TI  - Improved exercise capacity and reduced systemic inflammation after 
      adenoviral-mediated SERCA-2a gene transfer.
PG  - 257-65
LID - 10.1016/j.jss.2007.03.081 [doi]
AB  - BACKGROUND: We hypothesized that sarcoplasmic reticulum Ca2+ ATPase pump 
      (SERCA-2a) gene delivery would have beneficial effects upon exercise capacity and 
      markers of inflammation in the setting of heart failure. MATERIALS AND METHODS: A 
      pressure-overload model of experimental heart failure was used in rats. Following 
      a decrease in fractional shortening of >or=25%, animals underwent intracoronary 
      adenoviral-mediated gene transfection using SERCA-2a. Heart failure animals were 
      randomized to receive the SERCA-2a gene, the beta galactosidase (control) gene, 
      or followed without any further intervention. Exercise and hemodynamic testing 
      were performed, and myocardial and systemic markers of inflammation were assayed 
      after 7 and 21 d. RESULTS: Animals receiving Ad.SERCA-2a showed an increase in 
      exercise tolerance (499.0 +/- 14.9 versus 312.8 +/- 10.5 s, P < 0.0001) relative 
      to Ad.Gal group. Groups treated with Ad.SERCA-2a had significantly decreased 
      serum levels of the inflammatory markers interleukin-1, interleukin-6, and tumor 
      necrosis factor-alpha compared with Ad.Gal-treated animals. Serum levels of 
      atrial natriuretic peptide were decreased in animals receiving Ad.SERCA-2a 
      compared with animals receiving Ad.Gal at day 7 (0.35 +/- 0.03 versus 0.52 +/- 
      0.11 pg/mL, P = 0.001). Myocardial levels of the proapoptotic protein bax were 
      reduced in Ad.SERCA-2a -treated animals compared with those receiving Ad.Gal at 
      day 7 (protein level/actin: 0.24 +/- 0.05 versus 0.33 +/- 0.04, P = 0.04) and day 
      21 (protein level/actin: 0.61 +/- 0.04 versus 0.69 +/- 0.01, P = 0.001). 
      CONCLUSIONS: Genetic modulation of heart failure using the SERCA-2a gene was 
      associated with improvement in cardiac function and exercise capacity as well as 
      improvements in heart-failure associated inflammatory markers.
FAU - Gupta, Dipin
AU  - Gupta D
AD  - Department of Cardiac and Thoracic Surgery, Temple University School of Medicine, 
      Philadelphia, Pennsylvania 19140, USA.
FAU - Palma, Jon
AU  - Palma J
FAU - Molina, Ezequiel
AU  - Molina E
FAU - Gaughan, John P
AU  - Gaughan JP
FAU - Long, Walter
AU  - Long W
FAU - Houser, Steven
AU  - Houser S
FAU - Macha, Mahender
AU  - Macha M
LA  - eng
PT  - Journal Article
DEP - 20080211
PL  - United States
TA  - J Surg Res
JT  - The Journal of surgical research
JID - 0376340
RN  - 0 (Biomarkers)
RN  - EC 3.6.3.8 (Sarcoplasmic Reticulum Calcium-Transporting ATPases)
SB  - IM
MH  - Adenoviridae/genetics
MH  - Animals
MH  - Apoptosis
MH  - Biomarkers/metabolism
MH  - Cardiomyopathies/immunology/physiopathology/therapy
MH  - Diastole
MH  - Genetic Therapy/*methods
MH  - Heart Failure/immunology/physiopathology/*therapy
MH  - Heart Rate
MH  - Inflammation/immunology/physiopathology/*therapy
MH  - Male
MH  - Myocardium/pathology
MH  - *Physical Conditioning, Animal
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Sarcoplasmic Reticulum Calcium-Transporting ATPases/*genetics
MH  - Systole
MH  - Water-Electrolyte Imbalance
EDAT- 2008/02/12 09:00
MHDA- 2008/04/18 09:00
CRDT- 2008/02/12 09:00
PHST- 2006/12/28 00:00 [received]
PHST- 2007/03/21 00:00 [revised]
PHST- 2007/03/24 00:00 [accepted]
PHST- 2008/02/12 09:00 [pubmed]
PHST- 2008/04/18 09:00 [medline]
PHST- 2008/02/12 09:00 [entrez]
AID - S0022-4804(07)00242-9 [pii]
AID - 10.1016/j.jss.2007.03.081 [doi]
PST - ppublish
SO  - J Surg Res. 2008 Apr;145(2):257-65. doi: 10.1016/j.jss.2007.03.081. Epub 2008 Feb 
      11.