Objective— Adipocyte fatty acid-binding protein (A-FABP) abundantly expressed in mature adipocytes and activated macrophages has dramatic effects on atherosclerosis in mice. Whether this pathophysiological role of A-FABP may also apply to atherosclerotic disease in humans is still unknown. This study investigated associations among serum A-FABP levels, cardiovascular risk factors, and long-term secondary cardiovascular disease (CVD) outcome in patients with coronary heart disease. Methods and Results— Serum A-FABP levels were measured in 1069 patients with prevalent coronary heart disease and a 10-year prospective follow-up was conducted (median, 119.5 [interquartile range, 74.1–120.6] months). During this period 204 patients (incidence, 24.0/1000 patient-years) experienced a secondary cardiovascular disease event (defined as cardiovascular death, nonfatal myocardial infarction, or nonfatal cerebrovascular stroke). At baseline, circulating A-FABP was positively associated with a cluster of metabolic and inflammatory risk factors and independently predicted the presence of the metabolic syndrome (odds ratio per unit increase of natural log-transformed A-FABP, 2.95; 95% CI, 2.22–3.92, P <0.001). On long-term follow-up, subjects with high baseline A-FABP showed an increased risk for secondary cardiovascular disease events (hazard ratio per unit increase, 1.52; 95% CI, 1.18–1.95; P =0.001), which was attenuated after multivariable adjustment (hazard ratio 1.30; 95% CI, 0.98–1.73). In contrast, A-FABP remained significantly associated with cardiovascular death even after multivariable adjustment (hazard ratio, 1.75; 95% CI, 1.17–2.62, P =0.007). Conclusion— Circulating A-FABP levels are associated with long-term prognosis in patients with coronary heart disease and may represent an important pathophysiological mediator of atherosclerosis, which may point to a new target of treatment options.

Toll-like receptors (TLRs) are an evolutionarily conserved family of cell membrane receptors that are part of the innate immunity system playing an important role as a first response to tissue injury. TLR2 and TLR4 are constitutively expressed on renal epithelium, and their expression is enhanced following renal ischemia/reperfusion (I/R) injury. Genetic deletion of either TLR2 or TLR4 protects from renal I/R injury. However, it is not known whether deletion of both combined protects the kidney more than a deletion of either one alone. Therefore, we performed renal I/R injury in mice lacking TLR2, TLR4, and TLR2/4, respectively. Our results demonstrate that there are no significant differences regarding protection from renal I/R injury in TLR2/4((-/-)) compared with either TLR2((-/-)) or TLR4((-/-)) gene-targeted mice as determined by histological evaluation and renal functional parameters. Furthermore, there was no difference in the number of apoptotic tubular cells and in nuclear translocation of nuclear factor kappa-B (NF-kappaB) between the TLR-gene-targeted groups. In parallel, in vitro experiments did not demonstrate an additional effect of the double genetic deletion compared with the single gene deletion with respect to tumor necrosis factor (TNF)-alpha and interleukin (IL)-8 production in hypoxic isolated proximal tubular epithelial cells of the respective animals. In conclusion, a double genetic deletion of TLR2 and TLR4 confers a similar protection following renal I/R injury compared with single deletions of TLR2 and TLR4.