Imbalance between Platelet Vascular Endothelial Growth Factor and Platelet-derived Growth Factor in Pulmonary Hypertension

Abstract

Focal vascular injury and impaired endothelial function are features of pulmonary hypertension (PH) that lead to enhanced platelet endothelial cell interactions. Vascular endothelial growth factor (VEGF) is contained in platelets and released at sites of vascular injury to promote endothelial repair and wound healing in combination with platelet-derived nonspecific mitogens such as platelet-derived growth factor (PDGF). The overall balance between platelet VEGF and PDGF was investigated in 21 patients with primary PH, 8 with secondary PH, and 27 with chronic hypoxemic lung disease (CHLD), as well as in 29 control subjects. Platelet VEGF content was increased in patients with primary and secondary PH as compared with control subjects (518 +/- 89, 675 +/- 156, and 166 +/- 29 fg/10(5) platelets, respectively; p < 0.01), whereas platelet PDGF content was similar in the three groups (31 +/- 2, 36 +/- 4, and 33 +/- 3 pg/10(5) platelets, respectively; NS). Patients treated with a continuous prostacyclin infusion had a higher platelet VEGF but a similar platelet PDGF content as compared with untreated patients. Moderate increases in platelet VEGF and PDGF contents were observed in the CHLD patients. We conclude that patients with primary or secondary PH have an increase in platelet VEGF content, but not in platelet PDGF content, and that their platelet VEGF content increases further in response to prostacyclin infusion. We suggest that imbalance between platelet VEGF and PDGF is beneficial to patients with PH.

Growth factors and interleukin-6 across the lung circulation in pulmonary hypertension

“…In the current study, we did not find any correlation between VEGF and arterial or mixed venous oxygen saturation. Our results regarding circulating levels of VEGF agree with the findings in a previous report of elevated serum VEGF levels in peripheral venous blood samples from patients with PAH [22]. In contrast, BENISTY et al [23] showed no significant differences in circulating VEGF levels in peripheral venous blood samples between patients and control subjects.…”

Endothelial Dysfunction in Pulmonary Hypertension

“…Several trials have consistently shown an improvement in the exercise capacity, cardiopulmonary hemodynamics, New York Heart Association functional class, symptoms, as well as survival in patients with PAH treated with continuous infusion of intravenous prostacyclin (epoprostenol). [27][28][29] Epoprostenol infusion also improves the balance between ET-1 release and clearance, 30 increases VEGF levels, 31 and restores normal homeostasis by increasing plasma levels of soluble P-selectin and thrombomodulin, which are reportedly low in patients with PAH. 32…”

“…Platelet levels of VEGF are also elevated in PH. 31 The putative role of VEGF may depend on the very nature of the normal or diseased endothelial cells. In the resting or homeostatic state, VEGF is a survival and differentiating factor for lung endothelial cells and, therefore, VEGF elevation in PH may represent a protective response.…”

Interplay Between Serotonin Transporter Signaling and Voltage-Gated Potassium Channel (Kv) 1.5 Expression

“…Tryptophan hydroxylase (TPH), the rate-limiting enzyme in 5-HT biosynthesis, is also expressed at abnormally high levels in pulmonary endothelial cells from patients with idiopathic PAH, and therefore raises 5-HT levels locally . There is evidence that alterations in platelet 5-HT storage and/or increased platelet www.intechopen.com consumption by the lung may trigger the development of PAH (Herve et al, 1990;Herve et al, 1995;Breuer et al, 1996;Eddahibi et al, 2000b;Kereveur et al, 2000;Morecroft et al, 2005). Furthermore, serotoninergic appetite suppressant drugs have been associated with an increased risk of developing PAH (Douglas et al, 1981;Gurtner, 1985;Loogen et al, 1985;Brenot et al, 1993;Abenhaim et al, 1996;Souza et al, 2008).…”