Thromboxane A2 induces blood flow recovery via platelet adhesion to ischaemic regions

被引：29

作者：

Amano, Hideki ^{[1
]}

Ito, Yoshiya ^{[2
]}

Eshima, Koji ^{[3
]}

Kato, Shintaro ^{[1
,4
]}

Ogawa, Fumihiro ^{[1
]}

Hosono, Kanako ^{[1
]}

Oba, Kazuhito ^{[1
]}

Tamaki, Hideaki ^{[5
]}

Sakagami, Hiroyuki ^{[5
]}

Shibuya, Masabumi ^{[6
]}

Narumiya, Shuh ^{[7
]}

Majima, Masataka ^{[1
]}

机构：

[1] Kitasato Univ, Sch Med, Dept Pharmacol, Sagamihara, Kanagawa 2520374, Japan

[2] Kitasato Univ, Sch Med, Dept Surg, Sagamihara, Kanagawa 2520374, Japan

[3] Kitasato Univ, Sch Med, Dept Immunol, Sagamihara, Kanagawa 2520374, Japan

[4] Kitasato Univ, Sch Med, Dept Cardiol, Sagamihara, Kanagawa 2520374, Japan

[5] Kitasato Univ, Sch Med, Dept Anat, Sagamihara, Kanagawa 2520374, Japan

[6] Jobu Univ, Gakubunkan Inst Physiol & Med, Gunma, Japan

[7] Kyoto Univ, Grad Sch Med, Innovat Ctr Immunoregulat Technol & Drugs AK Proj, Kyoto, Kyoto, Japan

来源：

CARDIOVASCULAR RESEARCH | 2015年 / 107卷 / 04期

关键词：

Platelets; Thromboxane receptor; Angiogenesis; PSGL-1; P-selectin; ENDOTHELIAL GROWTH-FACTOR; BONE-MARROW; P-SELECTIN; ACTIVATED PLATELETS; INDUCED ANGIOGENESIS; TISSUE REGENERATION; TUMOR ANGIOGENESIS; HINDLIMB ISCHEMIA; PROGENITOR CELLS; IN-VIVO;

D O I：

10.1093/cvr/cvv139

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Aims Thromboxane A(2) (TXA(2)) induces platelet adhesion through thromboxane prostanoid (TP) receptor. Platelets contain many pro-angiogenic factors and are recruited to the site of vascular injury. However, the cellular and molecular mechanisms of platelet-dependent angiogenesis, especially the involvement of TP signalling, have not been fully elucidated. The present study hypothesized that TP-dependent platelet adhesion would contribute to angiogenesis in a mouse hindlimb ischaemic model. Methods and results Blood flow recovery was suppressed by the TXA(2) receptor antagonist (S-1452) and the TXA(2) synthase inhibitor (OKY-046) compared with control mice. TP knockout mice (TP-/-) showed delayed blood flow recovery from ischaemia and impaired angiogenesis compared with wild-type (WT) mice and prostacyclin receptor knockout mice (IP-/-). Selective platelet adhesion to ischaemic endothelial cells (ECs) via P-selectin was identified in WT and IP-/-, but not in TP-/-, via in vivo microscopy. IF analysis showed that P-selectin glycoprotein ligand-1 (PSGL-1) co-localized with endothelial CD31 in ischaemic muscle in WT and IP-/- but not diminished in TP-/-. Platelet-rich plasma levels of stromal cell-derived factor-1 and VEGF were increased after ischaemia in WT, and suppressed by antibody against P-selectin in WT but not in TP-/-. Furthermore, the blood flow recovery was suppressed by neutralizing antibodies against VEGF or C-X-C chemokine receptor type 4 in WT and IP-/- but not in TP-/-. Conclusion These results indicated that TP signalling facilitates ischaemia-induced angiogenesis via P-selectin-mediated platelet adhesion to PSGL-1 on the ECs at ischaemic sites and the supply of pro-angiogenic factors by the adherent platelets.

引用

页码：509 / 521

页数：13

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