The Relationship between the Transforming Growth Factorβ1 T29C Gene Polymorphism and Left Ventricular Geometry and Function in Hypertensive Subjects

The distribution of the T29C TGFβ1 gene polymorphism was analyzed in 198 hypertensives with left ventricular hypertrophy (LVH) and in 235 hypertensives without LVH. Circulating TGFβ1 levels, procollagen type III levels, microalbuminuria, and left ventricular geometry and function were evaluated in all the hypertensives with LVH subgrouped according to T29C TGFβ1 gene polymorphism. Circulating TGFβ1 was evaluated by ELISA technique, procollagen type III by a specific radioimmunoassay, microalbuminuria by radioimmunoassay, and left ventricular geometry and function by echocardiography. All groups were comparable for gender, age, and sex. Regarding T29C TGFβ1 gene polymorphism, prevalence of TC or CC genotypes was significantly (P<.05) higher in hypertensives with LVH than hypertensives without LVH TC and CC LVH hypertensives were characterized by a higher prevalence of subjects with microalbuminuria (P<.05TC and CC versus TT), by increased levels of TGFβ1, procollagen type III, urinary albumin excretion, LVM, LVM/h2.7, and lower values of left ventricular ejection fraction (P<.05TC and CC versus TT). Our data suggest that T29C TGFβ1 gene polymorphism was associated with clinical characteristics adequate to recognize a subset of LVH hypertensives with a higher severity of hypertension.

High Plasma Levels of Human Chromogranin a and Adrenomedullin in Patients with Pheochromocytoma

Aims and background The aim of our study was to investigate the plasma chromogranin A (CgA) and adrenomedullin (AM) levels in patients with pheochromocytomas. Methods and study design We collected blood samples for measurement of plasma CgA and AM in 21 patients with pheochromocytomas, 43 healthy subjects and 26 patients with solid non-functioning adrenocortical adenomas. In 11 patients with pheochromocytomas plasma CgA and AM were measured again four weeks after tumor removal. CgA and AM were measured by means of a novel solid-phase two-site immunoradiometric assay based on monoclonal antibodies (CgA-RIA CT, CIS bio international) and by a specific radioimmunoassay (RIA, Phoenix Pharm. Inc.), respectively. Results The mean plasma CgA level (±SD) in patients with pheochromocytomas (204 ± 147.9 ng/mL) was significantly higher (P <0.001) than that in healthy subjects (41.6 ± 10.7 ng/mL) and in patients with non-functioning adrenocortical adenomas (47.3 ± 17.6 ng/mL). The mean plasma AM concentration (±SD) in patients with pheochromocytomas (27.5 ± 10.4 pg/mL) was significantly higher (P <0.001) than that in HS (13.8 ± 4.5 pg/mL) and in patients with non-functioning adrenocortical adenomas (16.6 ± 7.3 pg/mL). Plasma CgA levels correlated with plasma AM levels (r = 0.501; P <0.02) and with plasma metanephrine levels (r = 0.738; P <0.0001) in patients with pheochromocytomas. In 11 patients with pheochromocytomas plasma CgA and AM concentrations significantly decreased after tumor removal (P <0.001 for both). Circulating CgA and AM had a sensitivity of 76.2% and 81%, a specificity of 97.7% and 90.7%, and an accuracy of 91% and 88%, respectively. Conclusion This study demonstrates that circulating CgA and AM levels are increased in pheochromocytoma patients compared with healthy subjects and patients with non-functioning adrenocortical adenomas. Moreover, at the time of diagnosis plasma CgA levels correlated with plasma AM levels and with plasma metanephrine levels in all patients with pheochromocytomas. In conclusion, plasma CgA and AM concentrations may represent additional biochemical parameters for clinical monitoring of patients with pheochromocytomas.

Developmental expression and biological activity of gastrin-releasing peptide and its receptors in the kidney

Mammalian gastrin-releasing peptide (GRP) has a widespread distribution and multiple stimulating effects on metabolism, release of regulatory peptides, gastrointestinal and pancreatic secretions, and behavior. GRP is a potent mitogen for a number of tumor types, including colon and lung. Although GRP is known to stimulate the growth of renal tumors, little is known of its synthesis, distribution, and receptors in the developing and mature kidney. Both Northern blot analysis and RT-PCR revealed the presence of GRP mRNA in ovine kidney from midgestation through to adulthood. GRP mRNA was detected in rat kidney from embryonic day 19 to postnatal day 30 by RT-PCR. Sequence-specific radioimmunoassay demonstrated the presence of substantial amounts of fully processed amidated GRP in the ovine renal cortex and medulla. The mRNA for the major receptor subtype, GRP-R, was present in fetal and adult sheep and rat kidneys. The mRNA for the low-affinity GRP receptor, bombesin receptor subtype-3 (BRS-3), was only detected in the rat kidney. In the ovine kidney, immunohistochemistry localized GRP predominantly to the thick ascending limb of the loop of Henle. mRNAs for GRP, GRP-R, and BRS-3 were detected in the human embryonic kidney cell line HEK293, and radioimmunoassay of cell extracts and conditioned media revealed the presence of proGRP but not the amidated form. However, amidated GRP did stimulate the proliferation of these cells. These studies demonstrate that the developing and mature kidney may be previously unidentified sites of autocrine or paracrine action for GRP.