Associations of inflammatory markers with impaired left ventricular diastolic and systolic function in collagen-induced arthritis.

BACKGROUND: High-grade inflammation may play a pivotal role in the pathogenesis of left ventricular (LV) dysfunction. Evidence to support a role of systemic inflammation in mediating impaired LV function in experimental models of rheumatoid arthritis (RA) remains limited. The aim of the present study was to determine the effects of high-grade systemic inflammation on LV diastolic and systolic function in collagen-induced arthritis (CIA). METHODS: To induce CIA, bovine type-II collagen emulsified in incomplete Freund's adjuvant was injected at the base of the tail into 21 three-month old Sprague Dawley rats. Nine-weeks after the first immunisation, LV function was assessed by pulsed Doppler, tissue Doppler imaging and Speckle tracking echocardiography. Cardiac collagen content was determined by picrosirius red staining; circulating inflammatory markers were measured using ELISA. RESULTS: Compared to controls (n = 12), CIA rats had reduced myocardial relaxation as indexed by lateral e' (early diastolic mitral annular velocity) and e'/a' (early-to-late diastolic mitral annular velocity) and increased filling pressures as indexed by E/e'. No differences in ejection fraction and LV endocardial fractional shortening between the groups were recorded. LV global radial and circumferential strain and strain rate were reduced in CIA rats compared to controls. Higher concentrations of circulating inflammatory markers were associated with reduced lateral e', e'/a', radial and circumferential strain and strain rate. Greater collagen content was associated with increased concentrations of circulating inflammatory markers and E/e'. CONCLUSION: High-grade inflammation is associated with impaired LV diastolic function and greater myocardial deformation independent of haemodynamic load in CIA rats.

Associations of inflammatory markers and vascular cell adhesion molecule-1 with endothelial dysfunction in collagen-induced arthritis.

We determined the role of high-grade inflammation on endothelial function and its association with biomarkers of endothelial dysfunction in collagen-induced arthritis. Sprague-Dawley rats were divided into a control (n = 12) or collagen-induced arthritis (CIA; n = 21) group. To induce arthritis, Bovine-type-II collagen emulsified in incomplete Freund's adjuvant was injected at the base of the tail. Nine-weeks after the primary immunisation, vascular reactivity in mesenteric and saphenous arteries was assessed using a wire-myograph. Serum concentrations of inflammatory markers (tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), interleukin 1ß (IL-1ß), C-reactive protein (CRP)) and biomarkers of endothelial dysfunction (vascular cell adhesion molecule-1 (VCAM-1) and asymmetric dimethylarginine (ADMA)) were measured by ELISA. Acetylcholine-induced relaxation in mesenteric and saphenous arteries was impaired in CIA compared to controls (P < 0.05). Responses to sodium nitroprusside were similar between controls and CIA in mesenteric arteries and marginally impaired in saphenous arteries of CIA rats. Compared to controls, TNF-α, IL-6, IL-1ß, CRP (all P < 0.00001) and VCAM-1 (P = 0.02) were elevated in CIA. TNF-α (std ß(SE) = 0.39(0.16); P = 0.03), IL-6 (std ß(SE) = 0.37(0.17); P = 0.03), IL-1ß (std ß(SE) = 0.41(0.16); P = 0.02) and CRP (std ß(SE) = 0.36(0.17); P = 0.04) were associated with VCAM-1. Associations between inflammatory markers and the maximal relaxation (Emax) to acetylcholine in mesenteric arteries were no longer significant after adjusting for VCAM-1 (except for IL-1ß). VCAM-1 was inversely associated with the Emax to acetylcholine in mesenteric (std ß(SE) = -0.49(0.16); P = 0.01) but not in saphenous arteries (std ß(SE) = -0.06(0.18); P = 0.76). In conclusion, exposure to high-grade inflammation impairs endothelial-dependent relaxation. The inflammation-induced increase in VCAM-1 concentrations may contribute to the impaired endothelium-dependent relaxation in mesenteric arteries of CIA rats.

Increased systolic blood pressure associated with hypertriglyceridemia in female Sprague-Dawley rats.

The effect of hyperlipidemia on the cardiovascular system is uncertain in females. The aim of the present study was to determine whether administration of a lipogenic diet alters cardiovascular parameters in female rats. Fifty female Sprague-Dawley rats were assigned into 2 groups of rats receiving a standard or a high-fat, high-sucrose diet (HFHS) for 6 weeks (n = 25 per group). Body mass, blood lipids concentrations, triglycerides clearance, blood pressures (BPs), systolic and diastolic functions, as well as vascular reactivity were assessed at the end of the diet intervention. At termination, body mass was similar between the 2 groups. Fasting blood triglycerides concentration (BTG) was greater in the HFHS group. Triglycerides clearance was impaired in the HFHS group. High-density lipoprotein (HDL) cholesterol concentration was lower in the HFHS group. The early-to-late diastolic filling velocity ratio (E/A) was lower in the HFHS group and negatively associated with BTG. The sensitivity (EC50) of mesenteric arteries to phenylephrine was greater in HFHS and was negatively associated with BTG, but not HDL. Systolic BP was higher in the HFHS group and was positively associated with BTG and HDL. The association between systolic BP and BTG was independent of other lipids measured. In conclusion, hypertriglyceridemia may have increased resistance arteries responsiveness to alpha-agonist and systolic BP in female rats.