Fibulin-1 and fibrinogen in human atherosclerotic lesions

Abstract

Fibulin-1 is a fibrinogen-binding blood protein and a component of many extracellular matrices (ECM) including those of blood vessels. In this study, the deposition patterns of fibulin-1 and fibrinogen were examined in human coronary artery atherosclerotic lesions excised by atherectomy from 20 patients. Fibulin-1 deposition was found to be closely overlapping with fibrinogen located within the atherosclerotic lesions and in regions containing fresh thrombi. Pronounced intracellular fibulin-1 immunostaining was apparent in lesion areas rich in macrophages and foam cells, although THP-1 macrophages and foam cells were found not to express fibulin-1. Strong ECM deposition of fibulin-1 was observed in acellular atheromatous and myxomatous regions. By contrast, fibulin-1 was present at relatively low levels in the ECM associated with smooth muscle cells within and outside of lesions and was not detected in sclerotic regions. These results reveal the pattern of fibulin-1 within human atherosclerotic lesions and highlight the potential for fibulin-1, perhaps derived from the blood and acting in conjunction with fibrinogen, to play a role in the etiology and cardiovascular disease progression, particularly with respect to thrombotic aspects of atherosclerosis.

Fibulin-1 Predicts Disease Progression in Patients With Idiopathic Pulmonary Fibrosis

“…23 In this study, as the levels of tissue fi bulin-1 increased, the lung function of the patients decreased. Given that fi bulin-1 is a known modulator of the ECM during the progression of some diseases, 24 this fi nding is indicative of the potential importance of fi bulin-1 as a target during fi brogenesis. Patients with IPF who presented with a high level of serum fi bulin-1 had a shorter progression-free survival time compared with those who had a low level of serum fi bulin-1.…”

Fibulin-1 Is a Marker for Arterial Extracellular Matrix Alterations in Type 2 Diabetes

“…Fibulin-1 deficiency in mice causes blood vessel abnormalities, particularly dilations and rupture, leading to massive hemorrhages and perinatal death (28,29 ). Little is known about the role of fibulin-1 in CVDs other than the fact that it is present in atherosclerotic lesions (30 ) and that its transcript is downregulated in aortic tissue from patients with aortic dissection compared to controls (31 ). Our observation of increased amounts of fibulin-1 in nonatherosclerotic tissue from diabetic patients adds to previous findings of arterial ECM accumulation in diabetes (5)(6)(7)(8).…”

Extending the knowledge in histochemistry and cell biology

“…Fibrinogen, Wbrin and Wbrin(ogen) degradation products are known components of atherosclerotic plaques (Libby et al 2006). Argraves et al (2009) recently further characterized deposition patterns of Wbulin-1 and Wbrinogen in human atherosclerotic lesions. In normal blood vessels, the Wbrinogen-binding protein Wbulin-1 is a component of the ECM (Tran et al 1995).…”