Propionyl-L-carnitine prevents age-related myocardial remodeling in the rabbit.
Age-related cardiac remodeling is characterized by changes in myocardial structure, which include fibrosis (ie, increased collagen concentration). The pathogenetic mechanisms of age-related cardiac changes and possible pharmacologic interventions are still a matter of investigation. A morphometric analysis of collagen accumulation was performed in Sirius Red-stained left ventricular sections of 3-month-old and 5-6-year-old animals after a 9-month period of propionyl-L-carnitine treatment (PLC; 120 mg Kg(-1) day(-1) per os); aged rabbits showed decreased interstitial collagen accumulation and no changes in cellularity and apoptotic rate compared to controls. Age-related expression of vascular cell adhesion molecule-1 (VCAM-1)-positive microvessels was also reduced in PLC-treated rabbits. In vitro, the 16-hour, 10-microM PLC treatment reduced collagen type 1 and VCAM-1 transcripts, which were investigated by reverse transcription-polymerase chain reaction, more markedly in cardiac fibroblasts from aged donors. In the latter, the anti-VCAM-1 antibody treatment was found to be associated with a reduction in collagen type I transcripts. Our results demonstrated that long-term PLC treatment partially prevents age-related interstitial remodeling and suggests that a more complex interstitial cell-to-cell signaling regulates senescent myocardium properties.
Orlandi
Augusto
A
Department of Biopathology and Image Diagnostics, Anatomic Pathology Institute, Tor Vergata University, Italy. orlandi@uniroma2.it
Francesconi
Arianna
A
Ferlosio
Amedeo
A
Di Lascio
Antonio
A
Marcellini
Marcella
M
Pisano
Claudio
C
Spagnoli
Luigi Giusto
LG
D000375:Aging / Q000502:physiology; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002331:Carnitine / Q000031:analogs & derivatives* / Q000494:pharmacology; D003094:Collagen / Q000187:drug effects / Q000378:metabolism; D024042:Collagen Type I / Q000187:drug effects; D004195:Disease Models, Animal; D004719:Endomyocardial Fibrosis / Q000188:drug therapy / Q000503:physiopathology; D005347:Fibroblasts; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D019010:Vascular Cell Adhesion Molecule-1 / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects*
D002316:Cardiotonic Agents; D024042:Collagen Type I; D019010:Vascular Cell Adhesion Molecule-1; C003223:propionylcarnitine; D003094:Collagen; D002331:Carnitine