Metabolism Division, Policlinico Universitario, via Giustiniani 2, 35128 Padova, Italy.
Nutr Metab Cardiovasc Dis. 2009 Dec;19(11):789-96. doi: 10.1016/j.numecd.2009.01.005. Epub 2009 Apr 5.
Hyperfibrinogenemia, a cardiovascular risk factor, is frequent in hypertension and largely unexplained. In this study, we measured fibrinogen production and whole-body protein turnover under both basal and hyperinsulinemic states, in hypertensive [H] and control [C] subjects, using a leucine stable isotope tracer and precursor-product relationships.
Since hypertension is often a feature of the "metabolic", insulin resistance syndrome, which in turn affects both fibrinogen kinetics and whole-body protein turnover, we selected hypertensive subjects without the metabolic syndrome. Following basal measurements, an euglycemic, approximately euaminoacidemic, hyperinsulinemic clamp was performed, with plasma insulin raised to 700-900 pmol/L. In H, rates of the fractional and absolute synthesis (FSR and ASR, respectively) of fibrinogen were 30%-40% greater (p<0.05 or less) than in C in both states, whereas leucine turnover was normal. Hyperinsulinemia did not modify fibrinogen synthesis in either group with respect to baseline, whereas it suppressed leucine appearance from endogenous proteolysis by approximately 40% to same extent in both groups. Amino acid clearance was similar in both the H and C subjects. In H, the insulin-mediated glucose disposal (M) was approximately 25% lower, (although insignificantly) than in controls, showing no overall insulin resistance. There was an inverse correlation between M and fibrinogen FSR during the clamp.
In essential hypertension fibrinogen production is increased, is not further stimulated by insulin, and is inversely related to insulin sensitivity at high-physiological insulin concentrations. Amino acid disposal and basal as well as insulin-responsive protein degradation rates are instead normal.
纤维蛋白原血症是心血管疾病的一个危险因素，在高血压中很常见，但很大程度上仍未得到解释。在这项研究中，我们使用亮氨酸稳定同位素示踪剂和前体-产物关系，在基础状态和高胰岛素状态下，测量了高血压[H]和对照组[C]受试者的纤维蛋白原生成和全身蛋白质周转率。
由于高血压通常是“代谢”胰岛素抵抗综合征的一个特征，而后者又影响纤维蛋白原动力学和全身蛋白质周转率，因此我们选择了没有代谢综合征的高血压受试者。在基础测量后，进行了一个正常血糖、近似正常氨基酸血症的高胰岛素钳夹实验，将血浆胰岛素提高到 700-900 pmol/L。在两种状态下，H 组的纤维蛋白原的分数和绝对合成率（FSR 和 ASR，分别）比 C 组高 30%-40%（p<0.05 或更低），而亮氨酸周转率正常。高胰岛素血症在两种情况下都没有改变纤维蛋白原的合成，而它抑制了内源性蛋白水解的亮氨酸出现，在两种情况下的程度相同。两种情况下氨基酸清除率相似。在 H 组中，胰岛素介导的葡萄糖处置（M）比对照组低约 25%（尽管无统计学意义），表明没有总体胰岛素抵抗。在钳夹过程中，M 与纤维蛋白原 FSR 呈负相关。
在原发性高血压中，纤维蛋白原生成增加，不再受胰岛素刺激，并且与高生理胰岛素浓度下的胰岛素敏感性呈负相关。氨基酸处置以及基础和胰岛素反应性蛋白质降解率正常。
