The effect of hormone therapy and raloxifene on serum matrix metalloproteinase-2 and -9 in postmenopausal women.

OBJECTIVE: The aim of the study was to investigate the effect of continuous-combined hormone therapy and raloxifene on the total and active forms of serum matrix metalloproteinase (MMP) -2 and -9. DESIGN: The study was double-blinded, with a placebo run-in period of 28 to 50 days. Twenty-eight women received either 17beta-estradiol 2 mg + norethisterone acetate 1 mg (E2/NETA) or raloxifene HCL 60 mg for a period of 6 months. Total and active forms of MMP-2 and -9 were estimated at baseline and at month 6. RESULTS: Total MMP-2 increased significantly in both E2/NETA and raloxifene groups (raloxifene baseline: 278.1 +/- 18.1 ng/mL; 6 months: 303.1 +/- 29.9 ng/mL, P = 0.008) (E2/NETA baseline: 281.9 +/- 27.5 ng/mL; 6 months: 298.8 +/- 12.7 ng/mL, P = 0.025). Similarly, both treatments increased the active MMP-2 fraction, although only the raloxifene-associated increase acquired significance (raloxifene baseline: 24.9 +/- 8.6 ng/mL; 6 months: 31.6 +/- 15.3 ng/mL, P = 0.045) (E2/NETA baseline: 21.7 +/- 5.7 ng/mL; 6 months: 27.4 +/- 5.8 ng/mL, P = 0.128). Total as well as active fractions of MMP-9 were not significantly affected by either treatment. CONCLUSIONS: Both E2/NETA and raloxifene increased the total and active MMP-2 serum levels. MMP-9 was not significantly affected by either regimen. Larger, long-term clinical trials are needed to elucidate the effect of HT and raloxifene on MMPs and the possible clinical implications for cardiovascular health.

The effect of Ca2+ channel antagonists on plasma concentrations of matrix metalloproteinase-2 and -9 in essential hypertension.

The ability of some antihypertensive drugs to protect from vascular damage in hypertension might be partially due to their ability to control matrix metalloproteinase (MMP)-mediated extracellular matrix metabolism, which in turn may contribute to vascular remodeling. This study was designed to investigate whether treatment with felodipine or diltiazem has any effect on plasma levels of MMP-2 and MMP-9 in essential hypertensive patients. We measured plasma levels of active MMP-2 and MMP-9 in 72 hypertensive subjects and 45 controls, both before and after 6 months of treatment with felodipine (group A) or diltiazem (group B). Mean adjusted differences, before and after each treatment, for MMP-2 and MMP-9 levels were: 19.8 (P =.01) for MMP-2, 0.2 (P =.5) for MMP-9 (group A), and 1.4 (P =.4) for MMP-2, 0.2 (P =.7) for MMP-9 (group B). These findings show that MMP-2 level is raised by treatment with felodipine but not diltiazem, whereas MMP-9 is unaffected by either treatment.

Basic fibroblast growth factor changes in response to coronary angioplasty in patients with stable angina.

Basic fibroblast growth factor (bFGF) has been implicated in the pathogenesis of coronary atherosclerosis and in angiogenesis. We assessed the changes in serum bFGF before, immediately after, and 6 months after coronary angioplasty (PTCA). Using the ELISA methods we measured plasma bFGF in 28 patients who underwent PTCA, in 20 patients with coronary artery disease who underwent elective coronary angiography and in 28 healthy subjects. Before PTCA and coronary angiography, bFGF plasma levels were similar in both patient groups (4.4+/-1.0 vs. 3.3+/-0.5 pg/ml), but were significantly higher compared with those of the control group (0.8+/-0.1 pg/ml, P<0.05). By 24 h, 3 months and 6 months after PTCA, bFGF levels had decreased significantly in the PTCA group (3.2+/-0.6, 1.7+/-0.3 and 2.7+/-0.6 pg/ml, respectively, P<0.05). In conclusion, these findings show that bFGF levels are elevated in patients with coronary artery disease. Following PTCA, bFGF levels decreased significantly and remained stable for 6 months after the procedure. Thus, bFGF level may change in response to PTCA in patients with coronary artery disease and stable angina.

Changes in maternal serum thioredoxin (TRX) levels after delivery in preeclamptic and normotensive pregnant women.

OBJECTIVE: To investigate changes of maternal plasma thioredoxin (TRX) levels after delivery in preeclamptic and normotensive pregnant women. METHODS: Ten normotensive women (group A) were compared to 17 women with severe preeclampsia (group B). TRX levels were assessed in maternal plasma, immediately after delivery and 12-16 weeks postpartum. RESULTS: There were no differences in plasma TRX levels between the two groups immediately antepartum (p = 0.095). A significant reduction in plasma TRX levels was found immediately following delivery only in normotensive group (117.76 ± 37.19 ng/mL vs. 43.45 ± 21.11 ng/mL, p = 0.002), but not in women with preeclampsia (80.42 ± 59.95 ng/mL vs. 53.82 ± 44.34 ng/mL, p = 0.12). Plasma TRX levels remained unchanged in women with preeclampsia (80.42 ± 59.95 ng/mL vs. 55.37 ± 52.23 ng/mL, p = 0.2) at 12-14 weeks postpartum.

Low-grade systemic inflammation profile, unrelated to homocysteinemia, in obese children.

To investigate in prepubertal obese children (POC) the profile of chronic low-grade systemic inflammation (CLGSI) and its relation to homocysteinemia, 72 POC were evaluated for serum C-reactive protein (CRP) and amyloid A (SAA) levels, both markers of CLGSI, and plasma levels of total homocysteine (tHcy), an independent risk factor for adult atherosclerosis, in comparison to 42 prepubertal lean children (PLC). The main observations in POC were higher CRP levels compared to PLC, positive association of SAA levels to CRP levels, no association of CRP or SAA levels to tHcy levels. Thus, in POC, positively interrelated to each other, elevated CRP and unaltered SAA levels reveal a unique profile of the CLGSI, not explaining homocysteinemia-induced risk for future atherosclerosis.

Negative association between circulating total homocysteine and proinflammatory chemokines MCP-1 and RANTES in prepubertal lean, but not in obese, children.

This study investigated in prepubertal obese children (POC), compared with prepubertal lean children (PLC), a possible relation among plasma total homocysteine (tHcy)-an independent risk factor for future atherosclerosis-and MCP-1 and RANTES, two circulating chemokines inducing leukocyte transendothelial migration (TEM), implicated in the initial stages of the inflammatory part of the atherosclerotic process. Seventy-two POC were evaluated for circulating tHcy, MCP-1, and RANTES, and compared with 42 healthy PLC. The mean adjusted (for age, sex as well as log10total insulin, vitB12, folate, total cholesterol, HDL cholesterol, log10triglycerides, and log10glucose levels) differences in tHcy, MCP-1, and RANTES levels between PLC and POC were all significant [1.16 nmol/mL (P = 0.03), 26.6 pg/mL (P = 0.02), and 52.9 pg/mL (P = 0.03), respectively]. In PLC, but not in POC, tHcy levels were negatively associated with both circulating MCP-1 (B = -1.68, P = 0.007) and RANTES (B = -1.16, P = 0.01) after adjusting for age, sex, BMI, as well as log10total insulin, vitB12, folate, total cholesterol, HDL cholesterol, log10triglycerides, and log10glucose levels. In conclusion, in POC there is a lack, in contrast to PLC, of a possibly autoregulatory, negative association of elevated tHcy levels to increased MCP-1 and RANTES levels. This could contribute to future, homocysteine-induced atherosclerosis.