Microfibrillar-associated protein 4 variation in symptomatic peripheral artery disease

Abstract

BackgroundSymptomatic peripheral artery disease (PAD) is an atherosclerotic occlusive disease affecting the lower extremities. The cause of symptomatic PAD is atherosclerosis, vascular dysfunctions, impaired angiogenesis and neointima formation. Microfibrillar-associated protein 4 (MFAP4) is an extracellular matrix protein, which is highly expressed in the heart and arteries and recently introduced as a potential mediator of pathological vascular remodeling and neointima formation. We aimed to investigate the relationship between serum MFAP4 (sMFAP4) and symptomatic PAD outcomes.MethodsA total of 286 PAD patients were analyzed if they had either intermittent claudication or critical lower-extremity ischemia (CLI) and followed for 7 years. The level of serum MFAP4 (sMFAP4) was measured by alphaLISA. Kaplan–Meier, Cox proportional hazard and logistic regression analysis were used to analyze the associations between upper tertile sMFAP4 and symptomatic PAD outcomes.ResultsPatients with upper tertile sMFAP4 had an odds ratio (OR) of 2.65 (p < 0.001) for having CLI diagnosis. Further analysis indicated that patients with upper tertile sMFAP4 had a hazard ratio (HR) of 1.97 (p = 0.04) for cardiovascular death during the 7-years follow-up. However, analysis of 2-year primary patency showed that patients with upper tertile sMFAP4 had decreased risk of vascular occlusion after reconstructive surgery with HR of 0.15 (p = 0.02).ConclusionssMFAP4 has potential as a prognostic marker for cardiovascular death, primary patency of reconstructed vessels and CLI diagnosis in symptomatic PAD patients. Confirmation of observations in larger cohorts is warranted.Electronic supplementary materialThe online version of this article (10.1186/s12967-018-1523-6) contains supplementary material, which is available to authorized users.

Relationship between Microfibrillar-Associated Protein 4 Levels and Subclinical Myocardial Damage in Chronic Kidney Disease

“…Another finding of our study was that the AR in our patient group was significantly greater than in the control group, and that this elevation was positively correlated with MFAP4. Previous experimental and clinical studies have both shown that MFAP4 is associated with vascular remodeling [10,23]. In the light of these findings, we think that MFAP4 may be associated with AR dilation in the patient group.…”

“…The authors interpreted this MFAP4 elevation as a potential marker of adaptive vessel wall alteration in chronic joint diseases. Hemstra et al [10] followed up 286 patients with peripheral artery disease for 7 years and suggested that serum MFAP4 levels were related to cardiovascular mortality, primary patency of reconstructed vessels in peripheral artery disease patients, and critical lower extremity ischemia, and that it might constitute a potential prognostic marker. In their study of 61 patients with paroxysmal atrial fibrillation (AF), 31 with persistent AF and 71 healthy controls, Zhang et al [16] determined higher MFAP4 levels in patients with AF than in healthy individuals and reported the highest MFAP4 levels in the persistent AF group.…”

“…MFAP4 binds to the extracellular matrix component elastin and collagen fibers and assists with the maintenance of vascular, pulmonary, cutaneous, and other connective tissue elasticity [8]. Studies have shown that serum levels of MFAP4 increase in chronic liver disease and various CVD, and particularly chronic obstructive pulmonary disease [7,[9][10][11]. However, we encountered no previous studies investigating MFAP4 levels in CKD.…”

Site‐specific absence of microfibrillar‐associated protein 4 (MFAP4) from the internal elastic membrane of arterioles in the rheumatoid arthritis synovial membrane: an immunohistochemical study in patients with advanced rheumatoid arthritis versus osteoarthritis

“…However, serological MFAP4 responses indicate that MFAP4 expression may adapt to specific demands, for example, in chronic liver disease . In addition, increased sMFAP4 has been shown to be a mortality predictor in cardiovascular disease .…”

“…The protein enhances elastic fiber formation and stimulates smooth muscle cell‐driven vascular and bronchial tissue hyperplasia . Increased circulating MFAP4 (sMFAP4) is a marker of mortality in cardiovascular disease . We hypothesized that MFAP4 can be detected in the synovial membrane from patients with advanced RA and aimed to compare the tissue distribution pattern with findings in patients with late stage OA.…”