Horgan Stephen J, Watson Chris J, Glezeva Nadia, Collier Pat, Neary Roisin, Tea Isaac J, Corrigan Niamh, Ledwidge Mark, McDonald Ken, Baugh John A
UCD Conway Institute of Biomolecular and Biomedical Research, UCD School of Medicine, University College Dublin, Belfield, Dublin, Ireland.
Chronic Cardiovascular Disease Unit, St. Vincent's University Hospital, Elm Park, Dublin 4, Ireland.
J Cardiovasc Transl Res. 2015 Dec;8(9):554-66. doi: 10.1007/s12265-015-9661-1. Epub 2015 Nov 17.
The potential for serum amyloid P-component (SAP) to prevent cardiac remodeling and identify worsening diastolic dysfunction (DD) was investigated. The anti-fibrotic potential of SAP was tested in an animal model of hypertensive heart disease (spontaneously hypertensive rats treated with SAP [SHR - SAP] × 12 weeks). Biomarker analysis included a prospective study of 60 patients with asymptomatic progressive DD. Compared with vehicle-treated Wistar-Kyoto rats (WKY-V), the vehicle-treated SHRs (SHR-V) exhibited significant increases in left ventricular mass, perivascular collagen, cardiomyocyte size, and macrophage infiltration. SAP administration was associated with significantly lower left ventricular mass (p < 0.01), perivascular collagen (p < 0.01), and cardiomyocyte size (p < 0.01). Macrophage infiltration was significantly attenuated in the SHR-SAP group. Biomarker analysis showed significant decreases in SAP concentration over time in patients with progressive DD (p < 0.05). Our results indicate that SAP prevents cardiac remodeling by inhibiting recruitment of pro-fibrotic macrophages and that depleted SAP levels identify patients with advancing DD suggesting a role for SAP therapy.
研究了血清淀粉样蛋白P成分（SAP）预防心脏重塑和识别舒张功能障碍（DD）恶化的潜力。在高血压性心脏病动物模型（用SAP治疗的自发性高血压大鼠[SHR-SAP]，治疗12周）中测试了SAP的抗纤维化潜力。生物标志物分析包括对60例无症状进行性DD患者的前瞻性研究。与用赋形剂处理的Wistar-Kyoto大鼠（WKY-V）相比，用赋形剂处理的SHR（SHR-V）的左心室质量、血管周围胶原、心肌细胞大小和巨噬细胞浸润均显著增加。给予SAP可使左心室质量（p<0.01）、血管周围胶原（p<0.01）和心肌细胞大小（p<0.01）显著降低。SHR-SAP组的巨噬细胞浸润显著减弱。生物标志物分析显示，进行性DD患者的SAP浓度随时间显著降低（p<0.05）。我们的结果表明，SAP通过抑制促纤维化巨噬细胞的募集来预防心脏重塑，而SAP水平降低可识别DD进展患者，提示SAP治疗具有一定作用。
