angiotensinogen and Lung-Diseases

Cerebrovascular stroke is a common critical complication of sickle cell disease (SCD). Angiotensinogen (AGT) M235T gene polymorphism is associated with risk of ischemic stroke and cardiovascular disease.. We investigated the potential association between angiotensinogen M235T gene polymorphism and susceptibility to cerebrovascular and cardiopulmonary complications in adolescents with SCD.. Forty-six patients with SCD in steady state were studied stressing on history of stroke, hydroxyurea/chelation therapy, hematological profile, and echocardiographic findings. Polymerase chain reaction-based restriction fragment length polymorphism analysis was used to detect AGT M235T gene polymorphism. Fifty sex- and age-matched healthy controls were enrolled for assessment of M235T gene polymorphism pattern.. The distribution of AGT M235T gene polymorphism was similar between SCD patients and healthy controls. The frequency of T allele of AGT M235T gene polymorphism (TT and MT genotypes) was significantly higher among patients with history of manifest stroke (P < .001). Patients with TT and MT genotypes had higher incidence of cardiopulmonary complications (P = .041) as well as higher percentage of HbS (P < .001) and lower hemoglobin level (P = .008) compared with those with MM genotype. Serum ferritin, liver iron concentration, and cardiac T2* were not related to T alleles or genotypes. Logistic regression analysis revealed that M235T genotype was a significant independent factor related to the occurrence of stroke among patients with SCD (Odds Ratio 14.05, 95% confidence interval 3.82-28.91; P = .001).. AGT M235T gene polymorphism may represent a genetic modifier to vascular morbidities in Egyptian patients with SCD.

Topics: Adolescent; Age Factors; Anemia, Sickle Cell; Angiotensinogen; Case-Control Studies; Cerebrovascular Disorders; Egypt; Female; Gene Frequency; Genes, Modifier; Genetic Association Studies; Genetic Predisposition to Disease; Heart Diseases; Humans; Lung Diseases; Male; Phenotype; Polymorphism, Genetic; Risk Factors; Young Adult

To investigate whether an inflammatory response occurs in patients undergoing infrarenal aortic abdominal aneurysm repair, the localization and timing (ischemia and/or reperfusion) of this activation, and finally whether it affects postoperative pulmonary function.. Prospective, observational study.. Academic referral center in Italy.. We included 12 patients undergoing infrarenal aortic abdominal aneurysm repair and 12 patients undergoing major abdominal surgery.. Timed measurement of gene activation (angiotensinogen, angiotensin type 1 receptor, angiotensin-converting enzyme, and interleukin-6 genes) in muscle biopsies by reverse transcriptase-polymerase chain reaction (RT-PCR), and prospective assessment of interleukin-6 plasma concentration and pulmonary function (Pao2/FIO2 and Pao2/PAO2 ratios).. After 30 mins of aortic clamping, angiotensinogen, angiotensin type 1 receptor, angiotensin-converting enzyme, and interleukin-6 genes were all overexpressed at RT-PCR studies in quadriceps muscle of patients undergoing aortic abdominal aneurysm repair, and the overexpression persisted after reperfusion. In situ hybridization and immunohistochemistry revealed that the inflammatory response was localized in endothelial cells. A significant increase in plasma interleukin-6 concentrations was then detectable at 6 and 12 hrs after reperfusion in aortic abdominal aneurysm surgery compared with patients undergoing abdominal surgery (p < .05). The increase in interleukin-6 plasma concentration was then followed (12 and 24 hrs after surgery) by a significant reduction of Pao2/ FIO2 and Pao2/PAO2 ratios (p < .05 vs. abdominal surgery).. The present study shows that a) during aortic surgery, the genes for interleukin-6 and for the components of the local renin-angiotensin system (angiotensinogen, angiotensin-converting enzyme, and angiotensin type 1 receptor subtype) are activated early in the ischemic muscle, and activation persists during reperfusion; b) interleukin-6 plasma concentration increases only in patients with tissue ischemia (aortic abdominal aneurysm), whereas no changes are detectable in patients with abdominal surgery; and finally c) the occurrence of systemic inflammatory reaction with increased interleukin-6 plasma concentrations is followed by impaired pulmonary function.

Topics: Aged; Angiotensinogen; Aortic Aneurysm, Abdominal; Colectomy; Female; Gastrectomy; Gene Expression Regulation; Humans; Inflammation; Interleukin-6; Lung Diseases; Male; Middle Aged; Muscle, Skeletal; Nephrectomy; Peptidyl-Dipeptidase A; Postoperative Complications; Prospective Studies; Receptor, Angiotensin, Type 1; Renin-Angiotensin System; Reperfusion Injury; Systemic Inflammatory Response Syndrome; Thigh; Transcriptional Activation; Treatment Outcome