Fabio Pricolo

Matrix Metalloproteinase-2, -9, and Tissue Inhibitor of Metalloproteinase-1 in Patients with Hypertension

There are conflicting data in the literature regarding the expression pattern of the vascular matrix metalloproteinase (MMP) system and their inhibitors (TIMPs) in human hypertension. The authors hypothesized that MMP-2, MMP-9, and TIMP-1 would be abnormal in hypertension, reflecting alterations in extracellular matrix (ECM) turnover. The authors measured plasma levels and activities of MMP-2, MMP-9, and TIMP-1 in 44 hypertensive patients and 44 controls. MMP-2 levels and activity were significantly higher in hypertensive group (p < .0001). Significant increase was also observed for MMP-9 level and activity (p < .0001) and for TIMP-1 (p < .0001) in hypertensive patients. Plasma levels and activities of MMP-2, MMP-9, and TIMP-1 are increased in hypertensive patients, which may reflect abnormal ECM metabolism.

Metformin-pioglitazone and metformin-rosiglitazone effects on non-conventional cardiovascular risk factors plasma level in type 2 diabetic patients with metabolic syndrome.

Background and objective:  Metformin is considered the gold standard for type 2 diabetes treatment as monotherapy and in combination with sulphonylureas and insulin. The combination of metformin with thiazolidinediones is less well studied. The aim of the present study was to assess the differential effect, and tolerability, of metformin combined with pioglitazone or rosiglitazone on glucose, coagulation and fibrinolysis parameters in patients with type 2 diabetes mellitus and metabolic syndrome.

Telmisartan and Irbesartan Therapy in Type 2 Diabetic Patients Treated with Rosiglitazone: Effects on Insulin-Resistance, Leptin and Tumor Necrosis Factor-α

The aim of our study was to investigate the metabolic effect of telmisartan and irbesartan in subjects treated with rosiglitazone, a well-known insulin-sensitizing drug, in order to clarify the direct metabolic effects of the two former drugs. Patients were enrolled, evaluated, and followed at 3 Italian centers. We evaluated 188 type 2 diabetic patients with metabolic syndrome (94 males and 94 females in total; 49 males and 46 females, aged 56±5, treated with telmisartan; and 45 males and 48 females, aged 55±4, treated with irbesartan). All had been diabetic for at least 6 months, and glycemic control by the maximum tolerated dietary changes and maximum tolerated dose of oral hypoglycemic agents had been attempted and failed in all cases. All patients took a fixed dose of rosiglitazone, 4 mg/day. We administered telmisartan (40 mg/day) or irbesartan (150 mg/day) in a randomized, controlled, double-blind clinical manner. We evaluated body mass index (BMI), glycemic control (HbA1c, fasting plasma glucose and insulin levels [FPG, and FPI, respectively], and homeostasis model assessment [HOMA] index), lipid profile (total cholesterol [TC], low density lipoprotein-cholesterol [LDL-C], high density lipoprotein-cholesterol [HDL-C], and triglycerides [TG]), systolic and diastolic blood pressure (SBP and DBP), tumor necrosis factor-α (TNF-α), and leptin during the 12 months of this treatment. No BMI change was observed after 6 or 12 months in either group. Significant decreases in HbA1c and FPG were observed after 6 months in the telmisartan group, and after 12 months in both groups. The decrease in HbA1c and FPG at 12 months was statistically significant only in the telmisartan group. A significant decrease in FPI was observed at 12 months in both groups, and this decrease was significantly greater in the telmisartan group. Significant decreases in the HOMA index were observed at 6 and 12 months in both groups, and the decrease in the HOMA index after 12 months was significantly greater in the telmisartan group than in the irbesartan group. Significant changes in SBP, DBP, TC, and LDL-C were observed after 6 and 12 months in both groups. Significant decreases in TNF-α and leptin levels were observed after 6 months in the telmisartan group, and after 12 months in both groups. In conclusion, in this study of patients with type 2 diabetes mellitus and metabolic syndrome, telmisartan seemed to result in a greater improvement in glycemic and lipid control and metabolic parameters related to metabolic syndrome compared to irbesartan. These observed metabolic effects of different angiotensin type 1 receptor blockers could be relevant when choosing a therapy to correct metabolic derangement of patients affected by metabolic syndrome and diabetes.

Blood Pressure Control and Inflammatory Markers in Type 2 Diabetic Patients Treated with Pioglitazone or Rosiglitazone and Metformin

The aim of the study was to assess the effects of the combination of metformin plus pioglitazone or rosiglitazone on glucose and blood pressure in type 2 diabetic patients with metabolic syndrome, as well as its tolerability in those patients. In this 12-month, multicentric, double-blind, randomized, controlled, parallel-group trial, all patients began with metformin. Patients were randomized for self-administration of either pioglitazone or rosiglitazone for 12 months. We assessed body mass index (BMI), glycemic control (glycosylated hemoglobin [HbA1c], fasting and postprandial plasma glucose and insulin levels [FPG, PPG, FPI and PPI, respectively] and homeostasis model assessment [HOMA] index) and systolic and diastolic blood pressure (SBP and DBP, respectively), at baseline and at 3, 6, 9 and 12 months of treatment, as well as high-sensitivity C-reactive protein (hs-CRP), nitrites/nitrates and adiponectin (ADN) at baseline and at 12 months of treatment. Significant HbA1c decreases were obtained after 9 (p<0.05) and 12 (p<0.01) months in both groups. After 9 and 12 months, mean FPG and PPG levels were decreased in both groups (p<0.05 and p<0.01, respectively). We observed decreases in FPI and PPI at 9 and 12 months (p<0.05 and p<0.01, respectively) compared to the baseline values in both groups. Furthermore, HOMA index improvement over the baseline value was obtained only at 12 months (p<0.05) in both groups. SBP and DBP improved significantly (p<0.05, for each) in both groups after 12 months. hs-CRP decreased significantly (p<0.05) in both groups after 12 months; nitrites/nitrates and ADN increased significantly (p<0.05, for each) in both groups after 12 months. The combination of thiazolinediones and metformin is associated with a slight but significant improvement in the long-term blood pressure control of these patients, and with an improvement in the anti-inflammatory state, both of which are related to a similar reduction in insulin-resistance.

Thiazolidinedione Effects on Blood Pressure in Diabetic Patients with Metabolic Syndrome Treated with Glimepiride

The aim of our study was to compare the long-term effect of pioglitazone and rosiglitazone on blood pressure control of diabetic patients with metabolic syndrome treated with glimepiride. We evaluated 91 type 2 diabetic patients with metabolic syndrome. All were required to have been diagnosed as diabetic for at least 6 months, and to have failed to achieve glycemic control by dietary changes and the maximum tolerated dose of the oral hypoglycemic agents sulfonylureas or metformin. All patients took a fixed dose of 4 mg/day glimepiride. We administered pioglitazone (15 mg/day) or rosiglitazone (4 mg/day) for 12 months in a randomized, double-blind fashion, and evaluated body mass index (BMI), glycemic control, blood pressure and heart rate (HR) throughout the treatment period. A total of 87 patients completed the study and were randomized to receive double-blind treatment with pioglitazone or rosiglitazone. An increase in BMI was observed after 12 months (p<0.05) in both groups. After 9 and 12 months, there were significant decreases in glycated hemoglobin (HbA1c), mean fasting plasma glucose (FPG), postprandial plasma glucose (PPG), fasting plasma insulin (FPI), and postprandial plasma insulin (PPI) in both treatment groups (p<0.05 at 9 months and p<0.01 at 12 months for all parameters). Furthermore, homeostasis model assessment index (HOMA index) improvement was obtained at 9 and 12 months (p<0.05 and p<0.01, respectively) in both groups. Significant systolic blood pressure (SBP) and diastolic blood pressure (DBP) improvement (p<0.05, respectively) was observed in both groups after 12 months. There were no significant changes in transaminases at any point during the study. We can conclude that the association of a thiazolinedione to the glimepiride treatment of type 2 diabetic subjects with metabolic syndrome is associated to a significant improvement in the long-term blood pressure control, related to a reduction in insulin-resistance.

Effects of rosiglitazone and pioglitazone combined with metformin on the prothrombotic state of patients with type 2 diabetes mellitus and metabolic syndrome.

In this multicentre, randomized, double-blind, controlled, parallel-group trial, 103 patients with type 2 diabetes mellitus and metabolic syndrome were randomized to receive one of two thiazolidinediones – pioglitazone or rosiglitazone – in combination with 1500 mg/day of metformin, increasing up to 3000 mg/day, for 12 months. Anthropometric, metabolic, coagulation and fibrinolysis parameters were assessed at baseline and after 3, 6, 9 and 12 months. Significant decreases in glycosylated haemoglobin, fasting plasma glucose and post-prandial plasma glucose levels were seen after 9 and 12 months in both groups, and significant decreases in fasting plasma insulin and post-prandial plasma insulin levels were seen after 12 months in both groups. In both groups, improvement in the homeostasis model assessment index compared with baseline was obtained only after 12 months. Plasminogen activator inhibitor-1 levels were significantly lower in both groups after 12 months compared with baseline values. In patients with type 2 diabetes mellitus and metabolic syndrome, the combination of metformin plus thiazolidinediones improved glycaemic control and produced a slight but significant reduction in plasminogen activator inhibitor-1 levels.

Effect of doxazosin on c-reactive protein plasma levels and on nitric oxide in patients with hypertension

Inflammation has been hypothesized to play a role in the development of hypertension. The high-sensitivity C-reactive protein (hs-CRP) is a well-studied marker of systemic inflammation that has a predictive power with regard to the development of hypertension. This study was designed to test the hypothesis that hs-CRP plasma levels are altered in hypertension. Moreover, the study was to assess whether chronic antihypertensive treatment with doxazosin would normalize hs-CRP and nitrites/nitrates. We measured plasma levels of hs-CRP and nitrites/nitrates in 44 normotensive subjects and in 44 patients with hypertension before and after doxazosin therapy for 4 months. hs-CRP plasma levels were significantly higher (P<0.007) in untreated hypertensive group compared to controls. Significant decrease was observed for hs-CRP (P<0.05) in hypertensive patients after antihypertensive treatment. Nitrites/nitrates were significantly lower (P<0.0001) in the untreated hypertensive group compared to controls. A significant increase was observed for nitrites/nitrates (P<0.05) in hypertensive patients after antihypertensive treatment. These results suggest that doxazosin treatment exerts anti-inflammatory effects in addition to its antihypertensive properties in hypertensive patients.

Matrix Metalloproteinase-2, -9 and Tissue Inhibitor Metalloproteinase-1 in Patients with Hypertension Before and After Doxazosin Therapy

AbstractBackground: There are conflicting data in the literature regarding both the expression pattern of the vascular metalloproteinase (MMP) system and its tissue inhibitors (TIMPs) in human hypertension and the effect of antihypertensive drugs in modifying the MMP/TIMP system. This study was designed to test the hypothesis that MMP-2, MMP-9 and TIMP-1 are altered in hypertension reflecting alterations in extracellular matrix turnover. Moreover, the aim of the study was to assess whether chronic antihypertensive treatment with doxazosin would normalise these alterations. Materials and results: We measured plasma levels and activities of MMP-2, MMP-9 and TIMP-1 in 44 hypertensive patients before and after 4 months of doxazosin treatment. MMP-2 levels and activity were significantly lower in the hypertensive group after treatment (p < 0.0001) compared with respective values before treatment. Significant decrease was also observed for MMP-9 level and activity (p < 0.0001) and for TIMP-1 (p < 0.0001) in hypertensive patients after antihypertensive treatment. Conclusions: Plasma levels and activities of MMP-2, MMP-9 and TIMP-1 are decreased in hypertensive patients after treatment compared with respective values before treatment. This may demonstrate that antihypertensive drugs modify the MMP/TIMP system, contributing to the mechanisms of vascular remodelling.