Association Between Increased Estrogen Status and Increased Fibrinolytic Potential in the Framingham Offspring Study

Gebara, Otávio; Mittleman, Murray A.; Sutherland, Patrice; Lipinska, Izabella; Matheney, Travis; Xu, Ping; Welty, Francine K.; Wilson, Peter W.F.; Levy, Daniel; Muller, James E.; Tofler, Geoffrey H.

doi:10.1161/01.cir.91.7.1952

Cited by 268 publications

(156 citation statements)

References 48 publications

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“…Thus, increased accumulation of PAI-1 was observed in media of cultured aortic rings from cp/cp males even without addition of exogenous insulin. The lack of increased expression of PAI-1 by aortic rings from corpulent females is consistent with decreased vascular elaboration of PAI-1 in direct proportion to the circulating concentration of oestrogen, as reported in the Framingham Offspring Study [35].…”

Section: Discussionsupporting

confidence: 85%

Fibrinolysis and atherogenesis in the JCR:LA-cp rat in relation to insulin and triglyceride concentrations in blood

et al. 1998

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Fibrinolytic system proteins in blood and arterial walls [1±6] have been implicated in atherogenesis and in the macroangiopathy typical of non-insulindependent diabetes mellitus (NIDDM). Impairment of fibrinolysis may lead to accumulation of microthrombi that may induce or exacerbate atherogenesis. High concentrations of plasminogen activator inhibitor type-1 (PAI-1) and attenuated fibrinolytic activity are seen in human subjects with obesity, NID-DM, or both [7±10]. Obesity and particularly early stage NIDDM are also characterized by increased concentrations of immunoreactive insulin (IRI) evident in plasma. Several observations suggest a causal connection between hyperinsulinaemia, insulin resistance and impaired fibrinolysis in blood [7±10]. However, the temporal relationships between hyperinsulinaemia, hypertriglyceridaemia, and impaired fibrinolytic system capacity secondary to increased PAI-1 in blood and the onset of macroangiopathy have not yet been elucidated. Accordingly, we studied JCR:LA-cp (corpulent) rats, animals genetically predisposed to develop severe insulin resistance with hyperinsulinaemia, hyperlipidaemia, obesity, and subsequent macroangiopathy [11±14].The JCR:LA-cp atherosclerosis-prone rat strain is one in which many aspects of early NIDDM and atherogenesis are simulated [11±14]. This strain incorporates an autosomal recessive cp (corpulent) gene and JCR:LA-cp rats homozygous for the cp gene (cp/ cp) are obese, insulin resistant, and hypertriglyceridaemic [13]. Heterozygous ( + /cp) and homozygous Diabetologia (1998) Summary Increased concentrations of plasminogen activator inhibitor type-1 (PAI-1) in blood and attenuated fibrinolytic activity, hypertriglyceridaemia, and insulin resistance are common in subjects with obesity and non-insulin-dependent diabetes mellitus who are at markedly increased risk for coronary artery disease. To clarify potentially causal relationships between these phenomena, we studied JCR:LA-cp rats, animals that are insulin resistant and prone to vasculopathy. Blood and aortas were obtained from lean and corpulent animals at 1, 2, 4, 6, and 9 months of age. The homozygous corpulent rats were hyperinsulinaemic and hypertriglyceridaemic at all ages tested. Increased activity of PAI-1 was present in blood from corpulent animals at 1, 6, and 9 months of age. Positive correlations were observed between blood PAI-1 and both insulin and triglycerides. As judged from results with aortic rings in in vitro culture, the increased PAI-1 in blood was anteceded by increased expression of PAI-1 in arterial walls. Thus, changes indicative of inhibition of the fibrinolytic system capacity precede gross atherosclerosis.[ Diabetologia (1998) 41: 141±147]Keywords Atherosclerosis, diabetes, hyperinsulinaemia, hypertriglyceridaemia, plasminogen activator inhibitor-1.Received: 8 July 1997 and in revised form: 23 September 1997Corresponding author: Dr. P. M. Absher, Department of Medicine, Given Building, Room C-323, University of Vermont College of Medicine, Burlington, VT 05405,...

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Section: Discussionsupporting

confidence: 85%

Fibrinolysis and atherogenesis in the JCR:LA-cp rat in relation to insulin and triglyceride concentrations in blood

et al. 1998

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“…Reduced PAI-1 levels and higher t-PA levels after HRT have been reported, which can increase the fibrinolytic potential in these patients. [46][47][48] These results confirm that oral CEE plus MP can reduce AT-III levels, as we observed previously, whereas unopposed CEE or transdermal 17beta-estradiol associated with MP did not change AT-III levels. There is no evidence of activation of blood coagulation, since the AT-III level was not reduced below normal range, and the F1+2 elevation was only modest.…”

Section: Group C At-iii (%)supporting

confidence: 90%

Effect of Estrogen-Progestin Hormonal Replacement Therapy on Blood Coagulation and Fibrinolysis in Postmenopausal Women

Bonduki

Lourenço

Motta

et al. 2007

Clinics

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Tests were performed before (T0) and after 3 (T3), 6 (T6) and 12 (T12) months of treatment. AT was determined by an amidolytic method, whereas F1+2 and TAT complex were measured by ELISA. RESULTS: There was a significant reduction in the AT level of patients who received oral CEE plus MP at T3. There was no AT reduction in patients taking either oral CEE alone or transdermal 17beta-estradiol plus MP. F1+2 increased in all patients, but it reached statistical significance only in patients receiving transdermal 17beta-estradiol MP at T3. CONCLUSIONS: The CEE associated with MP treatment may reduce AT levels, whereas unopposed CEE or transdermal 17beta-estradiol plus MP does not change AT. These changes might not be clinically relevant in the general population; however, hormonal replacement therapy may increase the risk of thrombosis in women with congenital or acquired thrombophilia.

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“…However, one explanation has been proposed, in which differences in biology and physiology between the genders result in gender differences in the pathogeny, therapeutic effects and prognosis of CVD [40][41][42][43] . During menopause, women are at higher risk of cardiovascular disease due to the loss of the vascular protective effects of estrogen, which helps to prevent myocardial and vascular diseases 44,45) . In addition, Madonna M. Roche reported that CVD affects women with diabetes more significantly than men, especially when the disease is diagnosed at a later stage 46) .…”

Section: Discussionmentioning

confidence: 99%

Prevalence of High Arterial Stiffness and Gender-specific Differences in the Relationships with Classical Cardiovascular Risk Factors

Wen

Peng

Tang

et al. 2015

J Atheroscler Thromb

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Aim:To investigate the relationships between arterial stiffness and classic cardiovascular risk factors with respect to gender differences in addition to the prevalence of high arterial stiffness in Chongqing, China based on an examination of 18,336 subjects. Methods: The cardio-ankle vascular index was used as a marker of arterial stiffness. The relationships between arterial stiffness and body mass index (BMI) as well as metabolic syndrome (MetS) were estimated using logistic regression models. Results: The prevalence of high arterial stiffness was 12.74% in men and 9.91% in women. For age and BMI, compared with the reference group, men had higher adjusted odds ratios (ORs) in each group versus their female counterparts. For each individual index of MetS, the effects of waist circumference and systolic blood pressure (SBP) on high arterial stiffness exhibited remarkable gender differences, with women having higher ORs and adjusted ORs than men. As the sum of MetS traits increased, the ORs and adjusted ORs in the subjects also increased, with women having higher values than men in each group. Conclusions: Gender-specific differences exist in the prevalence of high arterial stiffness among subjects compared by age, BMI and MetS, with varying effects of influence for these factors between genders.J Atheroscler Thromb, 2015; 22: 706-717.

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Association Between Increased Estrogen Status and Increased Fibrinolytic Potential in the Framingham Offspring Study

Cited by 268 publications

References 48 publications

Fibrinolysis and atherogenesis in the JCR:LA-cp rat in relation to insulin and triglyceride concentrations in blood

Fibrinolysis and atherogenesis in the JCR:LA-cp rat in relation to insulin and triglyceride concentrations in blood

Effect of Estrogen-Progestin Hormonal Replacement Therapy on Blood Coagulation and Fibrinolysis in Postmenopausal Women

Prevalence of High Arterial Stiffness and Gender-specific Differences in the Relationships with Classical Cardiovascular Risk Factors

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