Coronary artery remodeling in a model of left ventricular pressure overload is influenced by platelets and inflammatory cells.
Left ventricular hypertrophy (LVH) is usually accompanied by intensive interstitial and perivascular fibrosis, which may contribute to arrhythmogenic sudden cardiac death. The mechanisms underlying the development of cardiac fibrosis are incompletely understood. To investigate the role of perivascular inflammation in coronary artery remodeling and cardiac fibrosis during hypertrophic ventricular remodeling, we used a well-established mouse model of LVH (transverse aortic constriction [TAC]). Three days after pressure overload, macrophages and T lymphocytes accumulated around and along left coronary arteries in association with luminal platelet deposition. Consistent with these histological findings, cardiac expression of IL-10 was upregulated and in the systemic circulation, platelet white blood cell aggregates tended to be higher in TAC animals compared to sham controls. Since platelets can dynamically modulate perivascular inflammation, we investigated the impact of thrombocytopenia on the response to TAC. Immunodepletion of platelets decreased early perivascular T lymphocytes' accumulation and altered subsequent coronary artery remodeling. The contribution of lymphocytes were examined in Rag1(-/-) mice, which displayed significantly more intimal hyperplasia and perivascular fibrosis compared to wild-type mice following TAC. Collectively, our studies support a role of early perivascular accumulation of platelets and T lymphocytes in pressure overload-induced inflammation.
Division of Cardiovascular Medicine, Gill Heart Institute, University of Kentucky, Lexington, Kentucky, USA.
Fanmuyi
F
Yang
Anping
A
Dong
Paul
P
Mueller
Jessica
J
Caicedo
Alyssa Moore
AM
Sutton
Juliana
J
Odetunde
Cordelia J
CJ
Barrick
Yuri M
YM
Klyachkin
Ahmed
A
Abdel-Latif
Susan S
SS
Smyth
D000818:Animals; D001792:Blood Platelets / Q000502:physiology*; D003331:Coronary Vessels / Q000473:pathology*; D015150:Echocardiography, Doppler; D005434:Flow Cytometry; D006352:Heart Ventricles / Q000473:pathology* / Q000503:physiopathology; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D016133:Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000502:physiology*