Abstract |
Cardiac effects of human immunodeficiency virus (HIV) transactivator (Tat) are unclear, but Tat decreases liver glutathione (an important mitochondrial antioxidant) when ubiquitously expressed in transgenic mice (TG). With an alpha-myosin heavy chain promoter, Tat was selectively targeted to murine cardiac myocytes. One high-expression hemizygous ((+/-)Tat(high); 12 copies) and two low-expression ((+/-)Tat(lowA, B); 2-5 copies) TG lines were created. Cardiomyopathy was documented with increased left ventricle (LV) mass, ventricular expression of atrial natriuretic factor ( ANF) mRNA, mitochondrial ultrastructural defects, and myocardial depletion of glutathione. In (+/-)Tat(high) TGs, normalized LV mass (determined echocardiographically) increased 46% (90 days), 134% (240 days), and 96% (365 days) compared with wild-type littermates (WT). LV fractional shortening was decreased to 28% (90 days), 27% (240 days), and 19% (365 days). (+/-)Tat(low) LV mass was unchanged (<or=365 days). ANF in (+/-)Tat(high) ventricles (180 days) was twofold WT values. Glutathione was selectively decreased in (+/-)Tat(high) hearts (120 days). (+/-)Tat(high) hearts contained damaged mitochondria (>or=210 days); however, profound mitochondrial destruction occurred in homozygous (+/+)Tat(high) hearts (10 days) and the pups died (14 days). Tat caused cardiac dysfunction in this TG and may impact on cardiomyopathy in acquired immunodeficiency syndrome.
|
Authors | Scott M Raidel, Chad Haase, Natalie R Jansen, Rodney B Russ, Roy L Sutliff, Leonard W Velsor, Brian J Day, Brian D Hoit, Allen M Samarel, William Lewis |
Journal | American journal of physiology. Heart and circulatory physiology
(Am J Physiol Heart Circ Physiol)
Vol. 282
Issue 5
Pg. H1672-8
(May 2002)
ISSN: 0363-6135 [Print] United States |
PMID | 11959630
(Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
|
Chemical References |
- Antioxidants
- Gene Products, tat
- RNA, Messenger
- Atrial Natriuretic Factor
- Glutathione
- Ascorbic Acid
|
Topics |
- Animals
- Antioxidants
(analysis)
- Ascorbic Acid
(analysis)
- Atrial Natriuretic Factor
(genetics)
- Blotting, Western
- Cardiomyopathies
(etiology, physiopathology)
- Echocardiography
- Electrocardiography
- Gene Expression
- Gene Products, tat
(genetics, physiology)
- Gene Targeting
- Glutathione
(analysis, metabolism)
- Heart Ventricles
(metabolism, pathology)
- Mice
- Mice, Transgenic
- Microscopy, Electron
- Mitochondria, Heart
(pathology)
- Muscle, Skeletal
(chemistry)
- Myocardial Contraction
- Myocardium
(chemistry, metabolism, ultrastructure)
- Organ Specificity
- RNA, Messenger
(analysis)
|