Circulating fibroblast activation protein α is reduced in acute ischemic stroke

Abstract

BackgroundFibroblast activation protein α (FAP), a membrane glycoprotein with dipeptidyl-peptidase and collagenase properties, is expressed in atherosclerotic plaques and remodeling of the extracellular matrix based on fibrosis. Fibrosis is a main contributor of atrial cardiomyopathies. In acute MI, circulating FAP is associated with outcome. Here, we investigated the correlation of circulating FAP to echocardiographic parameters of atrial remodeling and neurological impairment in acute ischemic stroke.MethodsCirculating FAP plasma concentrations were determined by ELISA in 47 patients with acute stroke and 22 control patients without stroke. Echocardiography was performed in all participants. Laboratory analysis, National Institutes of Health Stroke Scale (NIHSS) scoring and prolonged Holter-ECG-monitoring were performed in all stroke patients.ResultsPatients with acute stroke had lower circulating FAP concentrations than the control cohort (92 ± 24 vs. 106 ± 22 ng/mL, P < 0.001). There was no difference between the circulating FAP concentration comparing stroke due to atrial fibrillation, embolic stroke of undetermined source (ESUS) or atherosclerotic origin. Septal atrial conduction time (sPA-TDI) and left atrial (LA) volume index to tissue Doppler velocity (LAVI/a‘) representing echocardiographic parameters of LA remodeling did not correlate with FAP concentrations (sPA-TDI: r = 0.123, p = 0.31; LAVI/a‘: r = 0.183, p = 0.132). Stroke severity as assessed by NIHSS inversely correlated with circulating FAP (r = −0.318, p = 0.04). FAP concentration had a fair accuracy for identifying stroke in the receiver operating characteristic (ROC) analysis (AUC = 0.710, 95% CI: 0.577–0.843). A FAP concentration of 101 ng/mL discriminated between presence and absence of stroke with a sensitivity of 72% and a specificity of 77%. Lower circulating FAP concentration was associated with cardio-cerebro-vascular events within 12 months after admission.ConclusionsOur study is the first to associate FAP with echocardiographic parameters of LA-remodeling and function. FAP did not correlate with sPA-TDI and LAVI/a‘. However, FAP was associated with stroke, neurological impairment, and cardio-cerebral events within 12 months. Therefore, FAP might enable individualized risk stratification in ischemic stroke.

Plasma fibroblast activation protein is decreased in acute heart failure despite cardiac tissue upregulation

“…Uitte de Willige et al, found a positive association between BMI and soluble FAP and thus higher soluble FAP levels with increasing BMI; however, they did not find an association between soluble FAP level and age or diabetes [ 48 ]. In addition, Sieweke et al, did not observe a correlation between FAP concentrations and age, and their results are in line with those of Tillmans et al [ 43 , 47 ]. In the present study in acute HF, we did not find an association between plasma FAP levels and those clinical variables that were significantly different between acute and chronic HF, such as age or BMI.…”

“…The origin of circulating FAP is still unknown, and previous studies have suggested that plasma FAP levels do not reflect expression levels in organ tissues [ 43 ]. However, this does not occur with genes that show expression patterns similar to those of FAP; published data indicate that these genes maintain the same trend in tissue and serum expressions [ 44 – 46 ].…”

Design, Synthesis, and Evaluation of 18F-Labeled Tracers Targeting Fibroblast Activation Protein for Brain Imaging

“…Fibroblast activation protein (FAP) is a type II transmembrane serine protease, belonging to the prolyl-specific serine oligopeptidase family, which is widely expressed on the surface of cancer related fibroblasts and tumor-associated macrophage in the tumor microenvironment, such as liver cancer, colorectal cancer, pancreatic cancer and ovarian cancer . FAP is also highly expressed in lesions characterized by interstitial tissue activation, such as infectious, inflammatory, fibrotic diseases and wound healing, , but not expressed or low expressed in normal tissues and benign tumor stroma. Therefore, FAP is a reliable biomarker for tumor and other diseases diagnosis, treatment, and predicting efficacy.…”