P‑selectin increases angiotensin II‑induced cardiac inflammation and fibrosis via platelet activation.
Platelet activation is important in hypertension‑induced cardiac inflammation and fibrosis. P-selectin expression significantly (P<0.05) increases when platelets are activated during hypertension. Although P‑selectin recruits leukocytes to sites of inflammation, the role of P‑selectin in cardiac inflammation and fibrosis remains to be elucidated. The present study aimed to investigate whether platelet‑derived P‑selectin promotes hypertensive cardiac inflammation and fibrosis. P‑selectin knockout (P‑sel KO) mice and wild‑type (WT) C57BL/6 littermates were infused with angiotensin II (Ang II) at 1,500 ng/kg/min for 7 days and then cross‑transplanted with platelets originating from either WT or P‑sel KO mice. P‑selectin expression was increased in the myocardium and plasma of hypertensive mice, and the P‑sel KO mice exhibited significantly (P<0.05) reduced cardiac fibrosis. The fibrotic areas were markedly smaller in the hearts of P‑sel KO mice compared with WT mice, as assessed by Masson's trichrome staining. In addition, α‑smooth muscle actin and transforming growth factor β1 (TGF‑β1) expression levels were decreased in the P‑sel KO mice, as assessed by immunohistochemistry. Following platelet transplantation into P‑sel KO mice, the number of Mac‑2 (galectin‑3)‑ and TGF‑β1‑positive cells was increased in mice that received WT platelets compared with those that received P‑sel KO platelets, and the mRNA expression levels of collagen I and TGF‑β1 were also increased. The results from the present study suggest that activated platelets secrete P‑selectin to promote cardiac inflammation and fibrosis in Ang II‑induced hypertension.
Department of Cardiology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.
Gaizhen
G
Liu
Department of Cardiology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.
Bin
B
Liang
Department of Cardiology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.
Xiaosu
X
Song
Department of Cardiology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.
Rui
R
Bai
Department of Cardiology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.
Weiwei
W
Qin
Department of Cardiology, Tianjin Port Hospital, Tianjin 300456, P.R. China.
Xu
X
Sun
Department of Cardiology, The First Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.
Yan
Y
Lu
Department of Cardiology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.
Yunfei
Y
Bian
Department of Cardiology, The First Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.
Chuanshi
C
Xiao
D000804:Angiotensin II / Q000097:blood / Q000378:metabolism*; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism; D005355:Fibrosis; D015870:Gene Expression; D006973:Hypertension / Q000139:chemically induced / Q000150:complications; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009205:Myocarditis / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D019007:P-Selectin / Q000235:genetics / Q000378:metabolism*; D015539:Platelet Activation
D019007:P-Selectin; D000804:Angiotensin II