CORRELATION BETWEEN VASCULAR INFLAMMATION MARKERS, DIASTOLIC DYSFUNCTION AND CARDIOVASCULAR RISK IN PATIENTS WITH TAKAYASU ARTERITIS

Objective: Takayasu arteritis (TAK) increases vascular stiffness and arterial resistance. Abnormal immune response is a crucial factor in the pathogenesis of TAK. Here, we investigated I) vascular and cardiac ultrasonography parameters as increased cardiovascular risk in TAK patients, compared to atherosclerotic patients; ii) Treg and Th17 cells frequencyin TAK-refractory patients treated with infliximab Design and method: Clinical, instrumental and biochemical data in patients with active TAK were compared in a case control study were compared to age- and sex-matched atherosclerotic patients. In a subpopulation of TAK patients, Treg/Th17 cells percentage was measured before (T0) and after 18 months (T18) of infliximab treatment. Echocardiogram, supraaortic Doppler ultrasound, and lymphocytogram were carried out in all patients. Histological and immunohistochemical analysis were performed to correlate vessel wall patho-morphology and clinical/laboratory results Results: TAK patients displayed increased aortic valve dysfunction and diastolic dysfunction compared to atherosclerosis. Moderate-to-severe aortic regurgitation correlates with the highest serum levels of uric acid in TAK patients. A significant increase in aortic stiffness was associated with peripheral T lymphocyte levels. Increase in CD3+CD4+ and CD8+ infiltration and High-mobility group box 1 (HMGB1) was significantly higher in TAK group. CD15+ neutrophils were significantly higher in TAK, suggesting an association with inflammation-related vascular damage. Flow cytometric Tregs percentage was significantly reduced in TAK patients. Interestingly, in patients treated with infliximab, this value significantly increased at T18 compared to T0. Concomitantly, the frequency of CD3+CD4+IL-17+ cells behaved in the opposite way: the higher number of Th17 cells observed in TAK patients at T0 compared to controls significantly decreased at T18 compared to T0. Supporting the specific pathogenetic mechanisms of vessel damage in TAK, we found an increased risk of cardiovascular disease that correlates directly with the degree of inflammatory cell infiltration in the vessel wall. Conclusions: These observations strengthen the clinical efficacy of infliximab in TAK patients, supporting the idea that biologic therapy may achieve a better control of TAK progression and help to stabilize the Treg/Th17 score toward values similar to those found in atherosclerotic patients

Objective: Takayasu arteritis (TAK) increases vascular stiffness and arterial resistance. Abnormal immune response is a crucial factor in the pathogenesis of TAK. Here, we investigated I) vascular and cardiac ultrasonography parameters as increased cardiovascular risk in TAK patients, compared to atherosclerotic patients; ii) Treg and Th17 cells frequencyin TAK-refractory patients treated with infl iximab Design and method: Clinical, instrumental and biochemical data in patients with active TAK were compared in a case control study were compared to age-and sex-matched atherosclerotic patients. In a subpopulation of TAK patients, Treg/ Th17 cells percentage was measured before (T0) and after 18 months (T18) of infliximab treatment. Echocardiogram, supraaortic Doppler ultrasound, and lymphocytogram were carried out in all patients. Histological and immunohistochemical analysis were performed to correlate vessel wall patho-morphology and clinical/ laboratory results Results: TAK patients displayed increased aortic valve dysfunction and diastolic dysfunction compared to atherosclerosis. Moderate-to-severe aortic regurgitation correlates with the highest serum levels of uric acid in TAK patients. A signifi cant increase in aortic stiffness was associated with peripheral T lymphocyte levels. Increase in CD3+CD4+ and CD8+ infi ltration and High-mobility group box 1 (HMGB1) was signifi cantly higher in TAK group. CD15+ neutrophils were signifi cantly higher in TAK, suggesting an association with infl ammation-related vascular damage. Flow cytometric Tregs percentage was signifi cantly reduced in TAK patients. Interestingly, in patients treated with infl iximab, this value signifi cantly increased at T18 compared to T0. Concomitantly, the frequency of CD3+CD4+IL-17+ cells behaved in the opposite way: the higher number of Th17 cells observed in TAK patients at T0 compared to controls signifi cantly decreased at T18 compared to T0. Supporting the specifi c pathogenetic mechanisms of vessel damage in TAK, we found an increased risk of cardiovascular disease that correlates directly with the degree of infl ammatory cell infi ltration in the vessel wall.
Conclusions: These observations strengthen the clinical effi cacy of infl iximab in TAK patients, supporting the idea that biologic therapy may achieve a better control of TAK progression and help to stabilize the Treg/Th17 score toward values similar to those found in atherosclerotic patients Objective: Rheumatoid arthritis (RA) is characterized by excess cardiovascular risk attributed to the chronic infl ammatory load in combination with the accumulation of traditional cardiovascular risk factors. RA is being currently perceived as a cardiovascular risk factor equivalent to type 2 diabetes mellitus (DM2), although recent relevant studies have provided confl icting results. The aim of the present study was to compare markers of micro-and macrovascular dysfunction between patients with relatively well-controlled RA and patients with DM2.

MICRO-AND MACROVASCULAR ALTERATIONS IN RHEUMATOID ARTHRITIS COMPARED TO TYPE 2 DIABETES MELLITUS: EVIDENCE OF SIMILAR DEGREE OF ORGAN DAMAGE
Design and method: Patients with RA who presented low levels of systemic infl ammation and patients with DM2, who were free from cardiovascular comorbidities including hypertension, were studied. A control group that comprised of healthy volunteers was additionally included. All participants underwent applanation tonometry (Sphygmocor device) to assess a) carotid-femoral pulse wave velocity (PWV), b) augmentation index corrected for 75 bpm (AIx@75), c) central systolic/diastolic blood pressure (cSBP/cDBP) as markers of large artery stiffening. Subendocardial viability ratio (SEVR) or Buckberg index was measured with the same device as a functional marker of microvascular myocardial perfusion. In addition, carotid ultrasound was applied to evaluate a) carotid intima-media thickness (cIMT), as a marker of systemic atherosclerosis, and b) beta-stiffness index, as a marker of local stiffness in the carotid arteries.

Results:
We studied 31 patients with RA at remission or low disease activity, 32 patients with DM2 and 69 controls matched for age and offi ce blood pressure. Signifi cant differences were observed in several outcomes of the study between patients and controls; by contrast, none of the studied parameters (PWV, AIx@75, cSBP/cDBP, cIMT, beta-stiffness index, and SEVR) signifi cantly differed between patients with RA and patients with DM2 (Table 1).

Conclusions:
Patients with RA present impaired markers of micro-and macrovascular dysfunction, even in the absence of cardiovascular comorbidities including hypertension and whilst at remission or low disease activity. Moreover, the degree of divergent micro-and macrovascular alterations in this well-characterized group of RA patients appears comparable to that associated with DM2. These fi ndings are line with the widely held perception that RA should be regarded as a novel cardiovascular risk factor equivalent to DM2.

ASTRAGALOSIDE IV INHIBITS H2O2-INDUCED APOPTOSIS IN H9C2 CELLS BY ATTENUATING OXIDATIVE STRESS AND MITOCHONDRIAL DAMAGE
Miaomiao Qi, Qiongying Wang, Runmin Sun, Li Tian, Jing Yu. Lanzhou University Second Hospital, Lanzhou, CHINA Objective: To investigate the effects and mechanisms of As-IV on H2O2-induced apoptosis in H9c2 cells.
Design and method: H9c2 cells were divided into three groups, including normal control group (cultured without intervention), H2O2 group (cultured with 200umol/L H2O2 for 2 hours), As-IV group (cultured with 100umol/L As-IV for 1 hour), As-IV with H2O2 group (pretreated with 100umol/L As-IV for 1 hour, then incubated with H2O2 for 2 hours). FITC/PI and DCFH-DA are stained to examine levels of apoptosis and ROS receptively. Levels of SOD and MDA were measured. Stained with JC-1 probe to observe the change of mitochondrial membrane potential (MMP). Western-blot was detected to analyze the expression of Drp-1.