Unsaturated fatty acids isolated from human lipoproteins activate protein phosphatase type 2Cβ and induce apoptosis in endothelial cells

Saturated, but Not Unsaturated, Fatty Acids Induce Apoptosis of Human Coronary Artery Endothelial Cells via Nuclear Factor-κB Activation

“…Even though respective data are lacking, it is conceivable that this stearate concentration can be reached in pathological situations associated with markedly increased lipolytic rates, such as morbid obesity and type 2 diabetes. The proapoptotic effects of saturated NEFAs on HCAECs is in agreement with earlier studies in HUVECs (5,6). In these cells, however, Artwohl et al (5) additionally demonstrated that unsaturated NEFAs, at a concentration of 300 mol/l, act proapoptotically as well.…”

“…In addition to these indirect proatherogenic properties, multiple direct effects of NEFA on cell types involved in atherogenesis are described: in endothelial cells, NEFAs induce the expression of cell adhesion molecules and inflammatory cytokines; in macrophages, NEFAs increase cholesterol uptake and reduce cholesterol efflux; and in arterial smooth muscle cells, NEFAs increase proliferation and migration (4). Interestingly, NEFAs also reveal proapoptotic effects in human umbilical vein endothelial cells (HUVECs) (5,6). Since increasing evidence, mainly from histological examinations, suggests endothelial cell apoptosis to play an important role in atherogenesis, plaque erosion, and acute coronary syndromes (7,8), we studied the susceptibility of endothelial and smooth muscle cells from human coronary arteries toward NEFA-induced apoptosis (lipoapoptosis).…”

Different mechanisms of saturated versus polyunsaturated FFA-induced apoptosis in human endothelial cells

“…To date, the pro-apoptotic activity of different FFAs has been examined primarily in immortalized endothelial cell lines (EA.hy926, ECV304) and human umbilical vein endothelial cells (HUVECs) (3)(4)(5)(6). Studies involving target tissues directly affected by the metabolic syndrome are rare (7,16,17) and have not been performed in EPCs.…”

“…Studies involving target tissues directly affected by the metabolic syndrome are rare (7,16,17) and have not been performed in EPCs. Hitherto, FFAsʼ chain length, degree of saturation, and/ or position of double bonds (3,7), p38 mitogen-activated protein kinase (p38 MAPK) (5,16), NF-kB (7,16), bcl-2 family members (3,4), and executioner caspases, i.e., caspase-3 and/or -7 (5,17,18) have been reported to be involved in the pro-apoptotic action of selected FFAs. Characterization of underlying mechanisms for a broad spectrum of both selected nutritional FFAs and different human endothelial cell types is missing as yet.…”

Role of lipase-generated free fatty acids in converting mesenteric lymph from a noncytotoxic to a cytotoxic fluid

“…However, Choi et al (6) found that palmitic acid can induce apoptosis of HUVECs and that the mechanism involves the dephosphorylation and activation of glycogen synthase kinase-3␤. Similarly, Hufnagel et al (21) found that treating lipoprotein with lipoprotein lipase liberated FFAs, especially linoleic and oleic acids, which induced the apoptosis of HUVECs by activating serine/threonine protein phosphatase type 2C and dephosphorylation of Bad. Others have found that treating postprandial plasma triglyceride-rich lipoprotein (VLDL and chylomicrons) with lipoprotein lipase results in increased levels of saturated and unsaturated FFAs, most pronouncedly linoleic acid and its hydroxylated metabolites, which are capable of inducing TNF-␣ and reactive oxygen species production in human aortic endothelial cells (36).…”