Browsing by Subject "ENDOTHELIAL DYSFUNCTION"

Sort by: Order: Results:

Now showing items 1-6 of 6
  • Benetos, Athanase; Bulpitt, Christopher J.; Petrovic, Mirko; Ungar, Andrea; Rosei, Enrico Agabiti; Cherubini, Antonio; Redon, Josep; Grodzicki, Tomasz; Dominiczak, Anna; Strandberg, Timo; Mancia, Giuseppe (2016)
  • Siltari, Aino; Korpela, R.; Vapaatalo, H. (2016)
    Bradykinin exerts its vascular actions via two types of receptors, the non-constitutively expressed bradykinin receptor type 1 (BR1) and the constitutive type 2 receptor (BR2). Bradykinin-induced vasorelaxation is age-dependent, a phenomenon related to the varying amounts of BR1 and BR2 in the vasculature. Isoleucine-proline-proline (Ile-Pro-Pro), a bioactive tripeptide, lowers elevated blood pressure and improves impaired endothelium-dependent vasorelaxation in hypertensive rats. It inhibits angiotensin converting enzyme 1 (ACE1). Other mechanisms of action have also been postulated. The aims of the study were to clarify the underlying mechanisms of the age-dependency of bradykinin-induced vasodilatation such as the roles of the two bradykinin receptors, themas-receptor and synergism with Ile-Pro-Pro. The vascular response studies were conducted using mesenteric artery and aorta rings from normotensive 6 wk. (young) and 22 wk. (old) Wistar rats. Cumulative dosing of acetylcholine, bradykinin and angiotensin(1-7) (Ang(1-7))were tested in phenylephrine-induced vasoconstriction with or without 10 min pre-incubation with antagonists against BR1-, BR2- or mas-receptors,Ang(1-7) or ACE1-inhibitors captopril and Ile-Pro-Pro. The bradykinin-induced vasorelaxation in vitro was age-dependent and it was improved by pre incubation with Ile-Pro-Pro, especially in old rats with endothelial dysfunction. The mas-receptor antagonist, D-Pro7-Ang(1-7) abolished bradykinin-induced relaxation totally. Interestingly, BR1 and BR2 antagonists only slightly reduced bradykinin-induced vasorelaxation, as an evidence for the involvement of other mechanisms in addition to receptor activation. In conclusion, bradykinin-induced vasorelaxation was age -dependent and He-Pro-Pro improved it. Mas receptor antagonist abolished relaxation while bradykinin receptor antagonist only slightly reduced it, suggesting that bradykinin-induced vasorelaxation is regulated also by other mechanisms than the classical BR1/BR2 pathway. (C) 2016 Elsevier Inc: All rights reserved.
  • Odermarsky, Michal; Pesonen, Erkki; Sorsa, Timo; Lernmark, Åke; Pussinen, Pirkko J.; Liuba, Petru (2018)
    This prospective study focuses on risk factors for arterial damage in children with type 1 diabetes (T1D). Eighty children and adolescents with T1D were investigated twice, approximately 2 years apart, for carotid artery intima-media thickness (cIMT) and compliance (CAC), flow-mediated dilatation (FMD) of the brachial artery, and plasma levels of matrix metalloproteinase (MMP)-8. All subjects were genotyped for HLA. The number of respiratory tract infections (RTI) during the past year was obtained by a questionnaire in 56 patients. cIMT progression, defined as percentage (%) change of cIMT from baseline, correlated inversely with the % changes of both CAC (p = 0.04, r = - 0.3; n = 62) and FMD (p = 0.03, r = - 0.3; n = 47). In multivariate analysis, RTI frequency correlated significantly with cIMT progression irrespective of age, diabetes duration, BMI, and HbA1c (p = 0.03, r = 0.3). When patients were divided in relation to RTI, the association of DQ2/8 with cIMT progression remained significant in patients with over three infections/year (p = 0.04, r = 0.3). During follow-up, the group of DQ2/8 patients with hsCRP > 1 mg/l showed significantly higher levels of plasma MMP-8 than the non-DQ2/8 group. The diabetes-risk genotype DQ2/8 and systemic inflammation contribute to pro-atherosclerotic vascular changes in children and adolescents with T1D.
  • Vilmi-Kerala, Tiina; Lauhio, Anneli; Tervahartiala, Taina; Palomaki, Outi; Uotila, Jukka; Sorsa, Timo; Palomaki, Ari (2017)
    Background: Gestational diabetes mellitus (GDM) has significant implications for the future health of the mother. Some clinical studies have suggested subclinical inflammation and vascular dysfunction after GDM. We aimed to study whether concentrations of high-sensitivity C-reactive protein (hsCRP), tissue inhibitor of metalloproteinase-1 (TIMP-1), matrix metalloproteinase-8 (MMP-8) and -9, as well as values of arterial stiffness differ between women with and without a history of GDM a few years after delivery. We also investigated possible effects of obesity on the results. Methods: We studied two cohorts-120 women with a history of GDM and 120 controls-on average 3.7 years after delivery. Serum concentrations of hsCRP were determined by immunonephelometric and immunoturbidimetric methods, MMP-8 by immunofluorometric assay, and MMP-9 and TIMP-1 by enzyme-linked immunosorbent assays. Pulse wave velocity (PWV) was determined using the foot-to-foot velocity method from carotid and femoral waveforms by using a SphygmoCor device. Arterial compliance was measured non-invasively by an HDI/PulseWave T CR-2000 arterial tonometer. All 240 women were also included in subgroup analyses to study the effect of obesity on the results. Multiple linear regression analyses were performed with adjustment for confounding factors. Results: PWV after pregnancy complicated by GDM was significantly higher than after normal pregnancy, 6.44 +/- 0.83 (SD) vs. 6.17 +/- 0.74 m/s (p = 0.009). Previous GDM was also one of the significant determinants of PWV in multiple linear regression analyses. On the other hand, compliance indices of both large (p = 0.092) and small (p = 0.681) arteries did not differ between the study cohorts. Serum TIMP-1 levels were significantly increased after previous GDM (p = 0.020). However, no differences were found in the serum levels of MMP-8, MMP-9 or hsCRP. In subgroup analyses, there were significantly higher concentrations of hsCRP (p = 0.015) and higher PWV (p <0.001) among obese women compared with non-obese ones. Conclusions: PWV values were significantly higher after GDM compared with normoglycemic pregnancies and were associated with prolonged TIMP-1 upregulation. Cardiovascular risk factors were more common in participants with high BMI than in those with previous GDM.
  • Finndiane Study Grp; Hägg-Holmberg, Stefanie; Dahlström, Emma H.; Forsblom, Carol M.; Harjutsalo, Valma; Liebkind, Ron; Putaala, Jukka; Tatlisumak, Turgut; Groop, Per-Henrik; Thorn, Lena M. (2019)
    Background: Hypertension is one of the strongest risk factors for stroke in the general population, while systolic blood pressure has been shown to independently increase the risk of stroke in type 1 diabetes. The aim of this study was to elucidate the association between different blood pressure variables and risk of stroke in type 1 diabetes, and to explore potential nonlinearity of this relationship. Methods: We included 4105 individuals with type 1 diabetes without stroke at baseline, participating in the nationwide Finnish Diabetic Nephropathy Study. Mean age at baseline was 37.411.9years, median duration of diabetes 20.9 (interquartile range 11.5-30.4) years, and 52% were men. Office systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured. Based on these pulse pressure (PP) and mean arterial pressure (MAP) were calculated. Strokes were classified based on medical and autopsy records, as well as neuroimaging. Cox proportional hazard models were performed to study how the different blood pressure variables affected the risk of stroke and its subtypes.ResultsDuring median follow-up time of 11.9 (9.21-13.9) years, 202 (5%) individuals suffered an incident stroke; 145 (72%) were ischemic and 57 (28%) hemorrhagic. SBP, DBP, PP, and MAP all independently increased the risk of any stroke. SBP, PP, and MAP increased the risk of ischemic stroke, while SBP, DBP, and MAP increased the risk of hemorrhagic stroke. SBP was strongly associated with stroke with a hazard ratio of 1.20 (1.11-1.29)/10mmHg. When variables were modeled using restricted cubic splines, the risk of stroke increased linearly for SBP, MAP, and PP, and non-linearly for DBP. Conclusions: The different blood pressure variables are all independently associated with increased risk of stroke in individuals with type 1 diabetes. The risk of stroke, ischemic stroke, and hemorrhagic stroke increases linearly at blood pressure levels less than the current recommended treatment guidelines.