title: Transcoronary gene transfer of SERCA2a increases coronary blood flow and decreases cardiomyocyte size in a type 2 diabetic rat model.
abstract: The Otsuka Long-Evans Tokushima fatty rat is an animal model of Type 2 diabetes mellitus (DM), which is characterized by diastolic dysfunction associated with decreased sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2a). The aim of this study was to examine whether gene transfer of SERCA2a can influence coronary blood flow and cardiomyocyte diameter in this model. DM rats were injected with adenovirus carrying SERCA2a (DM+SERCA) or beta-galactosidase gene (DM+betaGal). Coronary blood flow was measured in cross-circulated excised hearts 3 days after infection. Although in all groups coronary blood flow remained unchanged even if left ventricular (LV) volume or intracoronary Ca(2+) infusion was increased, the DM+SERCA group showed a sustained increase in coronary blood flow compared with the other groups. This result suggests that the sustained high coronary blood flow is a specific response in SERCA2a-overexpressed hearts. Although the LV weight-to-body weight ratio (LV/BW) and cardiomyocyte diameter were higher in the DM and DM+betaGal groups than in the non-DM group, in the DM+SERCA group, these measurements were restored to non-DM size. The percentages of collagen area in the three DM groups was significantly higher than results shown in non-DM rats, and there were no significant differences in collagen area percentage among the three DM groups. These results suggest that a lowered LV/BW by SERCA2a overexpression is due mainly to reduced size of cardiomyocytes without any changes in collagen area percentage. In conclusion, in DM failing hearts, SERCA2a gene transfer can increase coronary blood flow and reduce cardiomyocyte size without reduction in collagen production.
authors.affiliation: Cardiovascular Research Center, Massachusetts General Hospital, 149 13th St., CNY-4, Charlestown, MA 02129, USA.
authors.forename: Susumu
authors.initials: S
authors.lastname: Sakata
authors.forename: Djamel
authors.initials: D
authors.lastname: Lebeche
authors.forename: Yuri
authors.initials: Y
authors.lastname: Sakata
authors.forename: Naoya
authors.initials: N
authors.lastname: Sakata
authors.forename: Elie R
authors.initials: ER
authors.lastname: Chemaly
authors.forename: Lifan
authors.initials: L
authors.lastname: Liang
authors.forename: Chikako
authors.initials: C
authors.lastname: Nakajima-Takenaka
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Tsuji
authors.forename: Noboru
authors.initials: N
authors.lastname: Konishi
authors.forename: Federica
authors.initials: F
authors.lastname: del Monte
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Hajjar
authors.forename: Miyako
authors.initials: M
authors.lastname: Takaki
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D006332:Cardiomegaly / Q000209:etiology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D048429:Cell Size; D003094:Collagen / Q000378:metabolism; D003326:Coronary Circulation; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism*; D004195:Disease Models, Animal; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D008297:Male; D009200:Myocardial Contraction; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D011897:Random Allocation; D051381:Rats; D020334:Rats, Inbred OLETF; D020318:Rats, Long-Evans; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D003094:Collagen; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases