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J Transl Med. 2018 Jun 8;16(1):159. doi: 10.1186/s12967-018-1523-6.

Microfibrillar-associated protein 4 variation in symptomatic peripheral artery disease.

Author information

1
Cancer and Inflammation Research, Department of Molecular Medicine, University of Southern Denmark, J.B. Winsløws Vej 25, 3rd Floor, Odense, Denmark.
2
Cardiovascular Research Unit, Viborg Hospital, Viborg, Denmark.
3
Center of Individualized Medicine in Arterial Diseases (CIMA), Department of Cardiothoracic and Vascular Surgery, Odense University Hospital, Odense, Denmark.
4
Cancer and Inflammation Research, Department of Molecular Medicine, University of Southern Denmark, J.B. Winsløws Vej 25, 3rd Floor, Odense, Denmark. glsorensen@health.sdu.dk.

Abstract

BACKGROUND:

Symptomatic 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.

METHODS:

A 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.

RESULTS:

Patients 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).

CONCLUSIONS:

sMFAP4 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.

KEYWORDS:

Lower-extremity ischemia; MFAP4; Mortality; Peripheral artery disease; Primary patency

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