Thrombospondin-1 (TSP-1) is a potent endogenous inhibitor of both physiological and pathological angiogenesis, widely studied as a target in drug development for treating cancer. Several studies performed in the cardiovascular field on TSP-1 are contradictory, the role of TSP-1 in the physiopathology of cardiovascular disorders (CVDs) being, for the moment, incompletely understood and may be due to the presence of several domains in its structure which can stimulate many cellular receptors. It has been reported to inhibit NO-mediated signaling and to act on the angiogenesis, tissue perfusion, endothelial cell proliferation, and homeostasis, so we aimed to quantify the effect Perindopril has on TSP-1 plasma levels in hypertensive patients with endothelial dysfunction in comparison with other antihypertensive drugs, such as beta blockers, calcium channel blockers, and diuretics, in a chronic treatment. As a conclusion, patients under treatment with Perindopril had increased plasma levels of TSP-1 compared with other hypertensive patients and with the control group. The results of this study confirms the pleiotropic properties of Perindopril: anti-proliferative, anti-inflammatory, with effects showed by quantifying a single biomarker: TSP-1.
Purpose:
Endoglin is a transmembrane glycoprotein which plays an important role in maintaining cardiovascular homeostasis. One of its forms, soluble endoglin (sEng), a molecule with antiangiogenic properties, has been found overexpressed in patients suffering from hypercholesterolemia, diabetes mellitus and hypertension, and is proposed as a marker of endothelial damage. Accordingly, we aimed to quantify the efficacy of various antihypertensive regimens on sEng levels, in hypertensive patients with endothelial dysfunction.
Patients and methods:
323 patients were enrolled, and there were 99 patients with normal blood pressure values, 106 hypertensive patients under chronic treatment with different types of antihypertensive molecules (beta blockers, calcium channel blockers, and diuretics) in monotherapy, and 118 hypertensive patients under chronic treatment with perindopril. sEng plasma levels were quantified and were correlated with classical methods of assessing the endothelial damage.
Results:
Patients under chronic treatment with perindopril had lower sEng plasma levels compared with the other group of hypertensive patients under different regimens of antihypertensive treatment (sEng: 4.73±1.39 versus 5.63±2.33,
p
<0.01).
Conclusion:
Decreased sEng plasma levels were found in patients under chronic treatment with perindopril, when compared with other antihypertensive regimens of treatment (beta blockers, calcium channel blockers, and/or diuretics).
BackgroundThrombospondin-1 (TSP-1) is a matricellular functional protein of the extracellular matrix. As it is not constitutively present extracellularly, its secretion is enhanced in several situations, namely injury, chronic pathology, tissue remodeling, angiogenesis, and aging. Over the last decade, TSP-1 has been reported to be involved in complex and opposing biological effects on vasculature in the context of NO signaling. Several studies have reported high patient TSP-1 plasma levels, indicating that the protein can potentially serve as a prognostic marker for pulmonary arterial hypertension.Materials and methodsHere, we aimed to quantify TSP-1 serum levels in hypertensive patients with endothelial dysfunction before and after one year of treatment with Perindopril (an antihypertensive drug with vasoprotective properties).ResultsAfter one year of treatment, TSP-1 levels increased in hypertensive patients compared to baseline (T0: 8061.9 ± 3684.80 vs T1: 15380±5887 ng/mL, p<0.001) and compared to non-hypertensive controls (9221.03 ± 6510.21 ng/mL). In contrast, pentraxin-3 plasma levels were decreased after one year of Perindopril treatment in both hypertensive (T0: 0.91 ± 0.51 vs T1: 0.50 ± 0.24 ng/mL, p<0.001) and control group (1.36 ±1.5 ng/mL) patients, although flow-mediated vasodilation and intima-media thickness assessment parameters were not significantly changed. Systolic and diastolic blood pressure values as well as levels of fibrinogen, high-sensitivity C-reactive protein, triglycerides, and alanine aminotransferase were found to be significantly lower after one year of treatment with Perindopril. High levels of TSP-1 strongly correlated with platelet count (positive), lymphocytes (positive), red cell distribution width-CV (positive), systolic blood pressure (negative), and mean corpuscular hemoglobin (negative) after one year of treatment. Blood urea nitrogen was found to be a protective factor for TSP-1, while glucose and heart rate were found to be risk factors prior to and after treatment.
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