Aging and obesity augment the stress-induced expression of tissue factor gene in the mouse

Abstract

Hypercoagulability and thrombotic tendency are frequently induced by a variety of stressors. Clinically, aged subjects and obese patients are more susceptible to thrombotic diseases associated with stress, but the underlying mechanisms are unknown. We investigated the expression of a procoagulant gene, tissue factor (TF), in a mouse model of restraint stress.

Atherosclerosis and Vascular Aging as Modifiers of Tumor Progression, Angiogenesis, and Responsiveness to Therapy

“…Moreover, endothelial cells derived from these respective mice (even in the absence of tumors) were significantly impaired in their angiogenic capacity in vitro, as determined using the aortic ring-sprouting assay. Collectively, these results support and extend previous observations 26 -29 indicating that aging has a profound detrimental effect on endothelial cell properties, vascular integrity, 30,31 and angiogenic proficiency, including in cancer. 26 Although the apparent dysfunction of resident endothelial cells was consistently more severe in old/ApoE Ϫ/Ϫ mice than in their old/ApoE ϩ/ϩ counterparts, the respective differences did not reach statistical significance when applied to individual assays.…”

Vasculoprotective Effects of Anti-Tumor Necrosis Factor-α Treatment in Aging

“…2,13 Thus, both locally generated and circulating TNF-␣ ( Figure 1A) are likely to contribute to vascular aging phenotype. Our present data ( Figure 1A) and findings from previous studies suggest that plasma levels of TNF-␣ in elderly patients 9,10 and aged experimental animals 11,12 is probably in the range of ϳ0.3 ng/ml. It can be assumed that endothelial cells are exposed to even higher TNF-␣ concentrations attributable to the local release of TNF-␣ from cells within the vascular wall (smooth muscle cells, 2,3,13 leukocytes, and/or fibroblasts).…”

A functional polymorphism (−603A → G) in the tissue factor gene promoter is associated with adult-onset asthma

“…53 In mice studies, stress-induced expression of TF in several tissues was substantially higher in aged mice than in young mice. 54 Accordingly, TF expression in subjects with the À603GG genotype may be enhanced to a greater extent by aging when compared with the carriers of other genotypes, and adultonset asthma subsequently develops in these individuals, which is an alternative explanation for the heterogeneity of the genetic effects of the TF gene according to age at onset of the disease.…”