Abstract 18976: A Role of an HDL-associated Anti-inflammatory Protein, Progranulin, in Acute Coronary Syndrome
We previously reported that Progranulin (PGRN) is secreted from human monocyte-derived macrophages and bound to HDL/ApoA-I. Recently, we also demonstrated that PGRN deficiency leads to accelerated evelopment of atherosclerosis by generating ApoE-/-PGRN-/- (double knockout, DKO) mice compared with ApoE-/- mice. DKO mice exhibited enhanced systemic inflammation and impairment of endothelial function as well as excessive cholesterol accumulation in peritoneal macrophages. In addition, PGRN was mainly expressed in macrophages of atherosclerotic plaque. We hypothesized that PGRN may play some role in the coronary plaque stability in acute coronary syndrome. We enrolled consecutive patients (40 males and 11 females; mean age, 65.6±10.3 years) with ACS who underwent emergency coronary angiography. We also enrolled patients without coronary artery disease (79 male, 79 female; mean age, 61.8±13.5 years). There are not significant differences in peripheral blood PGRN concentration between two groups. We obtained peripheral vein blood samples, arterial blood samples as well as the aspirated samples obtained from the culprit lesion at the time of emergency PCI. Serial blood samples were obtained from on arrival to at discharge from the hospital and at the later outpatient visit. Immunostaining of aspirated samples showed that PGRN was mainly expressed in macrophages. Compared to peripheral vein and arterial samples, PGRN concentration in the coronary artery was significantly lower (47.9 ng/ml, 47.5 ng/ml vs 41.7 ng/ml,respectively). However, PGRN concentration gradually increased after PCI and became highest after 48 hours (47.9 ng/ml vs 59.7 ng/ml). We suggest that higher plasma PGRN concentration might stabilize the vulnerable plaque. We will show the in vitro studies using THP-1 cells and HAoSMC to demonstrate the effect of PGRN on the plaque stability such as MMP9 expression and fibrous cap formation. Taken together, HDL-associated anti-inflammatory protein PGRN may be involved in the stabilization of vulnerable coronary arterial plaques.
Author Disclosures: R. Kawase: Research Grant; Significant; Shionogi & Co., Ltd. : FLASH2012. Other Research Support; Significant; Otsuka Pharmaceutical Co., Ltd.. T. Ohama: None. M. Morita: None. Y. Kurozumi: None. N. Ito: None. T. Okada: None. D. Masuda: None. M. Koseki: None. M. Nishida: None. H. Sawano: None. Y. Doi: None. Y. Sakata: None. S. Yamashita: None.
- © 2014 by American Heart Association, Inc.