Long-term carperitide treatment attenuates left ventricular remodeling in rats with heart failure after autoimmune myocarditis.
The effect of carperitide, recombinant human atrial natriuretic peptide, on chronic heart failure (HF) has not been clarified. We investigated the beneficial effects of chronic carperitide treatment in rats with HF after experimental autoimmune myocarditis. A 28-day infusion of carperitide (n = 14) or vehicle (n = 14) was administrated to the rats 4 weeks after experimental autoimmune myocarditis induction. After 4 weeks, the myocardial levels of cyclic guanosine monophosphate (cGMP), left ventricular function, myocyte hypertrophy, interstitial fibrosis, myocardial capillary vessel density, and activity of one prominent substrate of cGMP, vasodilator-stimulated phosphoprotein (VASP) that may enhance angiogenesis, were measured. Carperitide treatment increased the myocardial levels of cGMP and attenuated the functional severity along with a decreased myocyte cross-sectional area, interstitial fibrosis, and an increased capillary to myocyte ratio. Furthermore, carperitide treatment enhanced the phosphorylation of VASP at Ser239, which was preferentially phosphorylated by cGMP-dependent protein kinase but not Ser157, which was preferentially phosphorylated by cyclic adenosine monophosphate-dependent protein kinase. Long-term carperitide treatment attenuates ventricular remodeling and ameliorates the progression of chronic HF. The effects of carperitide treatment are associated with increased neovascularization among the residual myocytes and an increase of VASP activation.
Tanaka
Komei
K
Division of Cardiology, Niigata University School of Medical and Dental Sciences, Niigata, Japan.
Ito
Masahiro
M
Kodama
Makoto
M
Hoyano
Makoto
M
Kimura
Shinpei
S
Mitsuma
Wataru
W
Hirono
Satoru
S
Adachi
Takeshi
T
Watanabe
Kenichi
K
Nakazawa
Mikio
M
Aizawa
Yoshifusa
Y
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000627:therapeutic use*; D001327:Autoimmune Diseases / Q000503:physiopathology*; D002196:Capillaries / Q000187:drug effects / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D048429:Cell Size / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects / Q000473:pathology; D006152:Cyclic GMP / Q000378:metabolism; D005355:Fibrosis; D006333:Heart Failure / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism; D009205:Myocarditis / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011897:Random Allocation; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000627:therapeutic use; D013318:Stroke Volume / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects*; D000098662:Vasodilator-Stimulated Phosphoprotein
D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; C472955:NPPA protein, human; D010750:Phosphoproteins; D011994:Recombinant Proteins; D000098662:Vasodilator-Stimulated Phosphoprotein; D009320:Atrial Natriuretic Factor; D006152:Cyclic GMP