Estrogen Signaling in Stroke Genetic and Experimental Studies

................................................................................................. 1 LIST OF ORIGINAL PAPERS .................................................................. 2 ABBREVIATIONS....................................................................................... 3 INTRODUCTION ....................................................................................5-29 Stroke ........................................................................................................ 5 Definitions and classifications ................................................................. 5 Etiology and pathophysiology ................................................................. 6 Ischemic stroke......................................................................................... 7 Intracerebral hemorrhage........................................................................... 8 Risk factors ............................................................................................... 8 Age and gender......................................................................................... 9 Hypertension ............................................................................................ 9 Smoking .................................................................................................. 9 Diabetes mellitus ...................................................................................... 9 Total serum cholesterol ........................................................................... 10 Serum triglycerides ................................................................................. 10 Body mass index (BMI) ....................................................................... 10 Genetics ................................................................................................... 11 Genetic variability .................................................................................. 11 Population genetics ................................................................................. 12 The northern Swedish population............................................................. 12 Prospective nested case-control studies .................................................... 13 Genotyping methods ............................................................................... 13 Genetics of stroke ................................................................................... 14 Monogenic stroke ................................................................................... 14 Polygenic stroke ..................................................................................... 14 Estrogen signaling .................................................................................. 15 Cardiovascular effects of estrogen signaling ....................................... 17 Estrogens and hypertension ..................................................................... 17 Estrogens and cerebral vasotension .......................................................... 18 Estrogens and serum lipids ...................................................................... 18 Estrogens and atherogenesis .................................................................... 18 Estrogens and hemostasis ........................................................................ 19 Estrogens and arterial calcification........................................................... 19 Estrogen signaling and stroke .................................................................. 19 The calcification paradox and stroke ........................................................ 20 Osteoprotegerin (OPG) ........................................................................... 20 OPG in arterial calcification and vascular diseases .................................... 21 Interleukin-6 (IL-6)................................................................................. 22