The place of estrogen in women's health remains controversial. Premenopausal women have a lower prevalence of cardiovascular disease (CVD) than men and in observational studies hormone replacement therapy (HRT) decreases CVD in postmenopausal women. However, prospective randomized trials of secondary and primary prevention have failed to substantiate an overall protective effect from HRT and have even shown some harm. To explain this paradox it is necessary to better understand the effects of estrogen on the vascular wall. Estrogen rapidly mediates the activation of eNOS and increases the production of nitric oxide (NO), an important factor for endothelial health. In ovariectomized rats estrogen reduces production of superoxide (O2-) by NAD(P)H oxidase. The decreased function is associated with a decrease in the p47phox component of NAD(P)H oxidase and its interaction with the multicomponent enzyme. In these rats estrogen did not alter eNOS expression and bioavailability of NO, which is in contrast to its acute effects. This highlights the difference between chronic and acute studies. The decrease in O2-production suggests the intracellular signaling. / Estrogen has antiapoptotic effects. Oxidized low-density lipoprotein (oxLDL) and the inflammatory cytokine TNFalpha increased apoptosis which is associated with atherosclerosis. In human umbilical vein endothelial cells (HUVEC), estrogen decreased the extent of TNFalpha and oxLDL induced apoptosis as indicated by the expression of cleaved caspase-3 and FACS assay. Estrogen also preserves the antiapoptotic mitochondrial Bcl-2 and Bcl-xL proteins. / Estrogen has angiogenic properties that can help a healthy endothelium respond to injury. However, estrogen increases the angiogenesis caused by TNFalpha and this could lead to revascularization in the plaques of women with advanced disease. / Overall the balance between the positive and negative aspects of the effects of estrogen on the vascular wall could explain the paradoxical response in older women.

Thesis (Ph. D.)--West Virginia University, 2007. / Title from document title page. Document formatted into pages; contains viii, 141 p. : ill. (some col.). Includes abstract. Includes bibliographical references.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2002. / Härtill 6 uppsatser.

Diss. (sammanfattning) Stockholm : Karol inst., 2003. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2002. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 4 uppsatser.