FKBPL is associated with metabolic parameters and is a novel determinant of cardiovascular disease

Abstract

Type 2 diabetes (T2D) is associated with increased risk of cardiovascular disease (CVD). As disturbed angiogenesis and endothelial dysfunction are strongly implicated in T2D and CVD, we aimed to investigate the association between a novel anti-angiogenic protein, FK506-binding protein like (FKBPL), and these diseases. Plasma FKBPL was quantified by ELISA cross-sectionally in 353 adults, consisting of 234 T2D and 119 non–diabetic subjects with/without CVD, matched for age, BMI and gender. FKBPL levels were higher in T2D (adjusted mean: 2.03 ng/ml ± 0.90 SD) vs. non-diabetic subjects (adjusted mean: 1.79 ng/ml ± 0.89 SD, p = 0.02), but only after adjustment for CVD status. In T2D, FKBPL was negatively correlated with fasting blood glucose, HbA1c and diastolic blood pressure (DBP), and positively correlated with age, known diabetes duration, waist/hip ratio, urinary albumin/creatinine ratio (ACR) and fasting C-peptide. FKBPL plasma concentrations were increased in the presence of CVD, but only in the non-diabetic group (CVD: 2.02 ng/ml ± 0.75 SD vs. no CVD: 1.68 ng/ml ± 0.79 SD, p = 0.02). In non-diabetic subjects, FKBPL was positively correlated with an established biomarker for CVD, B-type Natriuretic Peptide (BNP), and echocardiographic parameters of diastolic dysfunction. FKBPL was a determinant of CVD in the non-diabetic group in addition to age, gender, total-cholesterol and systolic blood pressure (SBP). FKBPL may be a useful anti-angiogenic biomarker in CVD in the absence of diabetes and could represent a novel CVD mechanism.

Characterisation of cardiac health in the reduced uterine perfusion pressure model and a 3D cardiac spheroid model, of preeclampsia

“…Therefore, ELISA was performed on rat heart protein lysates and immunofluorescent staining of sectioned tissue, which indeed confirmed an overall increase in FKBPL protein levels in RUPP hearts. This is aligned with the positive correlation observed previously between FKBPL plasma levels and diastolic dysfunction or BNP plasma levels in human samples [ 20 ]. Recent studies show that FKBPL regulates inflammatory STAT3 signalling, via CD44 and NFkB, which are both implicated in preeclampsia [ 26 , 53 , 64 , 65 ].…”

“…A novel anti-angiogenic protein, FK506-binding protein like (FKBPL), has recently been identified as having predictive and diagnostic roles in preeclampsia [ 19 ] as well as being a determinant of CVD [ 20 ]. FKBPL is a divergent member of the immunophilin group that shares similar structure and functions to the FKBP members but lacks an essential residue in its peptidyl prolyl isomerases (PPIase) domain preventing its ability to exert this catalytic activity [ 21 ].…”

E-cigarette Aerosol Condensate leads to Impaired Coronary Endothelial Cell Health and Restricted Angiogenesis

“…In relation to angiogenesis, although no changes were observed at the mRNA level, FKBPL at the protein level was signi cantly increased following exposure to nicotine e-Cig aerosol. Similarly, CD31 22,50 , was also increased following exposure to e-Cig aerosol with nicotine, perhaps as part of the compensatory mechanism. The determinant factor for these results appears to involve the presence of nicotine, which has been shown to have pro-angiogenic properties 14 .…”

Cognitive Impairment and Dementia: Gaining Insight through Circadian Clock Gene Pathways

“…However, additional risk factors for vascular dementia include hypertension, low education in early life, alcohol consumption, and tobacco use that can limit treatment efficacy [3,22,31,[59][60][61]. In regard to metabolic disorders, early diagnosis and treatment of DM may offer some degree of protection to inhibit disease progression, but tight serum glucose control cannot completely prevent the complications from DM [5,8,16,[62][63][64][65][66][67][68][69][70][71]. In light of the present challenges to overcome cognitive loss, innovative therapeutic strategies are necessary to develop new treatments for dementia.…”