In vivo flux of plasma cholesterol into human abdominal aorta with advanced atherosclerosis.

The mechanical properties of the aorta affect cardiac function and are related to cardiovascular morbidity/mortality. This study was designed to evaluate the isotropic (mainly elastin, elastiniso) and anisotropic (mainly collagen, collagenani) material parameters within the human aorta in vivo. Thirty healthy men and women in three different age categories (23–30, 41–54, and 67–72 yr) were included. A novel mechanical model was used to identify the mechanical properties and the strain field with aid of simultaneously recorded pressure and radius in the abdominal aorta. The magnitudes of the material parameters relating to both the stiffness of elastiniso and collagenani were in agreement with earlier in vitro studies. The load-bearing fraction attributed to collagenani oscillated from 10 to 30% between diastolic and systolic pressures during the cardiac cycle. With age, stiffness of elastiniso increased in men, despite the decrease in elastin content that has been found due to elastolysis. Furthermore, an increase in stiffness of collagenani at high physiological pressure was found. This might be due to increased glycation, as well as changed isoforms of collagen in the aortic wall with age. A marked sex difference was observed, with a much less age-related effect, both on elastiniso and collagenani stiffness in women. Possible factors of importance could be the effect of sex hormones, as well as differing collagen isoforms, between the sexes.

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Circulating Markers Reflect Both Anti- and Pro-Atherogenic Drug Effects in ApoE-Deficient Mice

Biomarker Insights ◽

10.4137/bmi.s632 ◽

2008 ◽

Vol 3 ◽

pp. BMI.S632 ◽

Cited By ~ 1

Author(s):

Birong Liao ◽

Eileen McCall ◽

Karen Cox ◽

Chung-Wein Lee ◽

Shuguang Huang ◽

...

Keyword(s):

Whole Blood ◽

Plasma Cholesterol ◽

Drug Effects ◽

Drug Efficacy ◽

Vascular Wall ◽

Atherosclerotic Plaques ◽

Protein Markers ◽

Novel Approach ◽

Coa Reductase

Background Current drug therapy of atherosclerosis is focused on treatment of major risk factors, e.g. hypercholesterolemia while in the future direct disease modification might provide additional benefits. However, development of medicines targeting vascular wall disease is complicated by the lack of reliable biomarkers. In this study, we took a novel approach to identify circulating biomarkers indicative of drug efficacy by reducing the complexity of the in vivo system to the level where neither disease progression nor drug treatment was associated with the changes in plasma cholesterol. Results ApoE-/- mice were treated with an ACE inhibitor ramipril and HMG-CoA reductase inhibitor simvastatin. Ramipril significantly reduced the size of atherosclerotic plaques in brachiocephalic arteries, however simvastatin paradoxically stimulated atherogenesis. Both effects occurred without changes in plasma cholesterol. Blood and vascular samples were obtained from the same animals. In the whole blood RNA samples, expression of MMP9, CD14 and IL-1RN reflected pro-and anti-atherogenic drug effects. In the plasma, several proteins, e.g. IL-1β, IL-18 and MMP9 followed similar trends while protein readout was less sensitive than RNA analysis. Conclusion In this study, we have identified inflammation-related whole blood RNA and plasma protein markers reflecting anti-atherogenic effects of ramipril and pro-atherogenic effects of simwastatin in a mouse model of atherosclerosis. This opens an opportunity for early, non-invasive detection of direct drug effects on atherosclerotic plaques in complex in vivo systems.

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SECRETION OF PROGESTERONE DURING GESTATION IN THE RAT

Journal of Endocrinology ◽

10.1677/joe.0.0790179 ◽

1978 ◽

Vol 79 (2) ◽

pp. 179-190 ◽

Cited By ~ 37

Author(s):

MRINAL K. SANYAL

Keyword(s):

Abdominal Aorta ◽

Primary Source ◽

Solvent System ◽

Peripheral Circulation ◽

Systemic Circulation ◽

Maternal Circulation ◽

Secondary Importance ◽

System Hexane ◽

Venous Plasma

The concentrations of progesterone and 5α-pregnane-3,20-dione in ovarian and uterine venous plasma and in the systemic circulation were measured during gestation in the rat. The steroids were quantified by radioimmunoassay after separation on silicic acid microcolumns with the solvent system hexane: ethyl acetate (5: 2, v/v). The concentration of progesterone in the systemic circulation was highest on days 3–4 and 13–17 of pregnancy; throughout gestation, the concentration of 5α-pregnane-3,20-dione was low in relation to that of progesterone and showed no marked changes as gestation proceeded. The level of progesterone in ovarian venous effluent was 10–20 times higher than that in the uterine vein and 20–50 times greater than that in the systemic circulation. The rate of secretion of progesterone by the ovary was highest during days 13–17 of gestation and ovariectomy during this period markedly reduced the levels of progesterone in the peripheral circulation. The concentration of progesterone in the uterine venous effluent was raised compared with the concentration in plasma from the abdominal aorta, especially on days 7 and 9 of pregnancy. These results suggest that, in vivo, the rat placenta synthesizes small amounts of progesterone and secretes it into the maternal circulation. The ovary is the primary source of progesterone during pregnancy and the placental contribution is of secondary importance. Although 4-ene-5α-reductase enzyme(s) is present in the ovary and placenta, significant quantities of the reduced progestin 5α-pregnane-3,20-dione are not secreted into the systemic circulation during gestation in the rat.

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