Percutaneous Intracoronary Delivery of Serca Gene Increases Myocardial Function: a Tissue-Doppler Imaging Echocardiographic Study

Autor: Damien Logeart, Jean-Baptiste Michel, Thierry Ragot, Jean-Jacques Mercadier, Michèle Heimburger, Brigitte Escoubet, Liliane Louedec, Laurent Vinet
Přispěvatelé: Vectorologie et transfert de gènes (VTG / UMR8121), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS)
Jazyk: angličtina
Rok vydání: 2006
Předmět:
medicine.medical_specialty
SERCA
Percutaneous
Physiology
Genetic enhancement
Cardiac Output
Low
Calcium-Transporting ATPases
030204 cardiovascular system & hematology
Doppler imaging
Gene Expression Regulation
Enzymologic
Ventricular Function
Left
Adenoviridae
Sarcoplasmic Reticulum Calcium-Transporting ATPases
03 medical and health sciences
0302 clinical medicine
[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system
Physiology (medical)
Internal medicine
medicine
Animals
Infusions
Intra-Arterial
[SDV.BBM]Life Sciences [q-bio]/Biochemistry
Molecular Biology
Gene
030304 developmental biology
0303 health sciences
Ventricular function
business.industry
Myocardium
Gene Transfer Techniques
Hemodynamics
Heart
Genetic Therapy
Myocardial function
Echocardiography
Doppler
Cardiology
Calcium
Rabbits
Cardiology and Cardiovascular Medicine
business
Zdroj: AJP-Heart and Circulatory Physiology
AJP-Heart and Circulatory Physiology, American Physiological Society, 2006,-, ⟨10.1152/ajpheart.00411.2006⟩
ISSN: 0363-6135
1522-1539
DOI: 10.1152/ajpheart.00411.2006⟩
Popis: The aim of this study was to examine the efficiency of adenovirus-mediated overexpression of sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA1a) gene in a realistic model based on percutaneous intracoronary delivery and on noninvasive functional monitoring. Catheter-based selective coronary delivery of saline or adenoviruses (Ad.CMV.SERCA1a or Ad.CMV.lacZ, 1010plaque-forming units) was performed in the circumflex artery of rabbits. Effects were assessed and compared by using serial Doppler echocardiography, hemodynamics, and measurements of SERCA protein and Ca2+uptake activity. On day 3, a 21% increase in SERCA proteins and a 37% increase in the maximal rate of Ca2+uptake were observed in the transfected left ventricular (LV) walls of Ad.CMV.SERCA1a rabbits. Baseline hemodynamics and conventional echographic measurements of global LV function were poorly affected. In contrast, tissue Doppler imaging (TDI) was able to assess a strong increase in the baseline function of transfected LV walls, as assessed with maximal wall velocities (+32% and +43%, respectively) and strain rates (+18% and +30%, respectively). TDI parameters were closely related to the maximal rate of Ca2+uptake ( r2= 0.68 for the systolic strain rate). Serial TDI analysis during follow-up showed that the effects lasted for 7 days and were no longer detectable 15 days after adenoviruses injection. In conclusion, LV function can be increased by adenovirus-mediated overexpression of SERCA in a clinically relevant model, and TDI provides an accurate and noninvasive tool for monitoring effects on global as well as regional myocardial function.
Databáze: OpenAIRE
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