Novel pro-atherogenic molecule coupling factor 6 is elevated in patients with stroke: A possible linkage to homocysteine

Abstract

CF6 is elevated in patients with stroke independently of risk factors. Since Hcy and vitamin treatment affect CF6 levels in stroke, CF6 appears to be a novel molecule for the pathogenesis and treatment of stroke.

Coupling factor 6-induced activation of ecto-F1Fo complex induces insulin resistance, mild glucose intolerance and elevated blood pressure in mice

“…2c). We and others had previously reported that the plasma level of CF6 was increased by twofold in patients with coronary heart disease, hypertension, end-stage renal disease and stroke, compared with that in healthy participants [13,[16][17][18][19]]. Thus, the plasma level of CF6 in transgenic mice was noted to be increased as compared with wild-type mice to a degree similar to that seen in patients with cardiovascular diseases.…”

“…5e, protons regulate cellular function by modulating the charge and structure of macromolecules, such as phosphorylation of RAC1 and dephosphorylation of insulin receptor, and also explain the activation of cSrc and p38 mitogen-activated protein kinase, the other signalling pathways of CF6 [21,32]. In clinical settings, we and others previously showed that circulating CF6 is elevated in patients with hypertension, acute myocardial infarction, end-stage renal disease, stroke and diabetes [13,14,[16][17][18], all of which predispose to the development of atherosclerosis. Given the present finding and the widespread biological actions of CF6, such as inhibition of prostacyclin and nitric oxide [21,[30][31][32][33], the reduction of CF6 levels may be an important and useful way to prevent cardiovascular events.…”

Coupling factor 6 attenuates CXCR4 expression through the HIF-1α and c-Src pathways and promotes endothelial apoptosis and inflammation

“…Given the present finding and the widespread biological actions of CF6, such as inhibition of prostacyclin and NO (8,9), reduction in CF6 levels may be important and useful to prevent arteriosclerosis and eventually cardiovascular events. To date, we have reported that salt restriction, vitamin C, and vitamin B 12 plus folic acid lower the plasma CF6 levels of patients with hypertension and stroke (13,14) and that peroxisome proliferator-activated receptor  ligand attenuate CF6 release from cultured vascular endothelial cells (33). Thus, the present findings may provide new insights into our understanding of the pivotal role played by CF6 in the mechanism underlying endothelial dysfunction.…”

“…In clinical settings, we and others have shown that circulating CF6 is elevated in patients with hypertension, acute myocardial infarction, end-stage renal disease, stroke, and diabetes (13,14,(29)(30)(31)(32), all of which are predispositions to arteriosclerosis. The present study showed that CF6 is involved in endothelial dysfunction and vascular impairment by downregulating CXCR4 signaling.…”

“…Figure 4A illustrates the representative bands for CXCR4 proteins in the hearts of TG and WT at 50 weeks of age. The immunoreactive band for CXCR4 at 40-47kD was decreased in the TG hearts compared with the WT hearts, and the ratio of CXCR4 to CF6 decreased the gene and protein expression of CXCR4, but the decrease was only significant at a concentration of more than 10 -7 M. Like other vasoactive substances, the plasma CF6 level (10 -9 -10 -8 M) was lower than the critical concentration (10 -7 M) at which CXCR4 expression in cultured vascular endothelial cells was decreased in vitro (13,14). We previously showed that intravenous administration of anti-CF6 antibody to rats counteracted the biological effects of CF6 (15).…”