Category Archives: Hypertension

Elevated Basic Fibroblast Growth Factor Levels: Effect of Therapy

Elevated Basic Fibroblast Growth Factor Levels: Effect of Therapy Effect of Therapy on Angiogenic Growth Factor Levels
The effect of medical therapy for PAH on growth factor levels was analyzed. Twelve patients (PPH, 6 patients; PAH-other, 6 patients) were not receiving prostanoid therapy, calcium-channel blockers, or endothelin blockers at the time of study (de novo patients). The median plasma bFGF level in this group of patients was significantly increased compared to control subjects (1.91 pg/mL, p = 0.02), as was the median urine bFGF level (2,338 pg/L, p = 0.002). The bFGF levels in these de novo patients were not significantly different from patients who were receiving specific therapy for PAH. Sixty-one percent of patients were receiving IV prostacyclin at the time samples were obtained for the cohort. Patients with PAH receiving prostacyclin had qualitatively higher median levels of plasma VEGF (42.9 pg/mL vs 25.4 pg/mL, p = 0. 09) than did patients not receiving prostacyclin, although this did not reach statistical significance. This trend remained when analyzed for the PPH subgroup (48.1 pg/mL vs 28.8 pg/mL, p = 0.13). When adjusted for covariates associated with severity of disease, the effect of prostacyclin on plasma VEGF was diminished, and prostacyclin was not independently associated with altered growth factor levels. Calcium-channel blocker therapy or anticoagulation with warfarin did not affect growth factor levels. Continue reading

Elevated Basic Fibroblast Growth Factor Levels: Plasma bFGF Levels

We examined the possibility that there may be a threshold level for urine bFGF. Using the 95th percentile in our control subjects as an upper limit of normal, we found that 21% of patients with PAH had elevations in urine bFGF. Twenty-six percent of patients with PPH, and 14% of patients with PAH-other (11% CHD and 19% CTD) had abnormally elevated urine bFGF levels (p = 0.008).
Median plasma levels of bFGF were significantly higher in patients with PAH than in control subjects (median, 1.9 pg/mL vs 0.5 pg/mL; p = 0.02). There was a difference in plasma bFGF levels based on etiology (PPH, 2.1 pg/mL; CHD, 1.7 pg/mL; CTD, 1.0 pg/mL; p = 0.3), but the only significant pairwise comparison was between PPH and control subjects (p = 0.05) [Fig 2, 3]. There was no significant difference between male and female patients. Continue reading

Elevated Basic Fibroblast Growth Factor Levels: Sample Collection and Assay

Elevated Basic Fibroblast Growth Factor Levels: Sample Collection and AssayBlood samples were collected in a plasma ethylenediamine tetra-acetic acid tube. Samples were centrifuged at 2,500g for 10 min, and plasma was collected and stored at — 80°C until it was assayed. Repeat freeze-thaw cycles were avoided. Spot urine specimens were obtained and stored at — 80°C until they were assayed. Measurements of VEGF and bFGF were performed, by batch, in duplicate, using an enzyme-linked immunoassay for VEGF and bFGF (Quantikine; R&D Systems; Minneapolis, MN). The coefficients of variation for bFGF were 10 to 14% for urine, and 9 to 11% for plasma. The coefficients of variation for VEGF were 4 to 7% for urine, and 5 to 7% for plasma. There was no significant cross-reactivity between the bFGF or VEGF antibodies and other known growth factors. Continue reading

Elevated Basic Fibroblast Growth Factor Levels: Materials and Methods

Although abnormal expression of bFGF and VEGF has been noted in animal models of pulmonary hypertension, their contribution to human PAH is not well understood. The detection of elevated growth factors in affected patients may help clarify the underlying mechanisms involved in the disease process. One area in which research on angiogenesis may have clinical application is the quantitation of angiogenesis. Quantitation of angiogenic proteins in body fluids has been used as an indirect measure of angiogenic growth factor activity in certain patients with tumors, as well as nonneoplastic diseases. We hypothesized that angiogenic growth factors may have a role in the cellular proliferation seen in the small vessels of the lung in PAH. We therefore measured bFGF and VEGF levels in the blood and urine of a large cohort of these patients. Continue reading

Elevated Basic Fibroblast Growth Factor Levels

Elevated Basic Fibroblast Growth Factor LevelsPulmonary arterial hypertension (PAH) is a devastating illness characterized by a pulmonary vasculopathy that gives rise to an elevation in pulmonary vascular resistance. There has been considerable debate regarding the mechanisms underlying the development of PAH. Although initially focused on vasoconstriction and factors modulating vasomotor tone in the pulmonary circulation, it has more recently been proposed that cellular proliferation of endothelial and smooth-muscle cells is a more central component of the histopathologic changes seen in this disease. The search for molecular pathways that are involved in this cellular proliferation is therefore of particular interest. Continue reading