Background: We investigated whether (1) monocrotaline(MCT)-induced right ventricular (RV) dilatation is associated with re-expression of myocardial tenascin-C (TNC), (2) elevated plasma TNC levels ...can be used as a marker of ventricular dilatation, and (3) MCT-induced RV dilatation is associated with alterations of other remodeling-related proteins. Methods: Rats were treated with MCT in low dose (30 mg/kg, MCT30, n=10) to induce compensated RV hypertrophy, in high dose (80 mg/kg, MCT80, n=11) to induce RV failure, and with saline as control (CONT, n=9). After 4 weeks, RV function was assessed. TNC gene expression, protein levels, and plasma levels were assayed. Myocardial gene expression of integrin subunit α6 and β1, and myocardial proMMP2 and proMMP9 levels were assessed. Results: TNC gene expression in the RV of MCT80 rats was significantly upregulated compared with RV of CONT (4-fold, p<0.001) and MCT30 rats (3-fold, p<0.01), whereas TNC gene expression was very low in LV and IVS of MCT80 rats, and absent in those of CONT and MCT30 rats. Myocardial TNC protein levels were only observed in MCT80 rats, and were higher in RV (0.62±0.64 ng/mg) than in LV (0.21±0.44 ng/mg) or IVS (0.21±0.09 ng/mg) (p<0.01, RV vs LV and IVS). Plasma levels of TNC were significantly elevated in MCT80 rats compared with CONT (p<0.05). RV volumes correlated positively with TNC plasma levels and RV ejection fraction correlated negatively with TNC plasma levels. MCT-induced RV failure was also associated with a significant downregulation of integrin α6 gene expression (by 48%, p<0.01). Conclusions: MCT-induced RV failure is associated with an upregulation of TNC gene expression, resulting in re-expression of myocardial TNC protein levels, and elevated TNC plasma levels. As RV ejection fraction correlated significantly with TNC plasma levels, TNC plasma levels may serve as a marker of ventricular failure. De-adhesive properties of TNC in combination with a downregulation of integrin α6 may have caused cardiomyocyte slippage, leading to adverse ventricular remodeling.
Recent advances in molecular resonance imaging of atherosclerosis enable to visualize atherosclerotic plaques in vivo using molecular targeted contrast agents. This offers opportunities to study ...atherosclerosis development and plaque vulnerability noninvasively. In this review, we discuss MRI contrast agents targeted toward atherosclerotic plaques and illustrate how these new imaging platforms could assist in our understanding of atherogenesis and atheroprogression. In particular, we highlight the challenges and limitations of the different contrast agents and hurdles for clinical application. We describe the most promising existing compounds to detect atherosclerosis and plaque vulnerability. Of particular interest are the fibrin-targeted compounds that detect thrombi and, furthermore, the contrast agents targeted to integrins that allow to visualize plaque neovascularization. Moreover, vascular cell adhesion molecule 1-targeted iron oxides seem promising for early detection of atherosclerosis. These targeted MRI contrast agents, however promising and well characterized in (pre)clinical models, lack specificity for plaque vulnerability.
Abstract only
Objective
Cardiac resynchronization therapy (CRT) has proven efficacy in improving left ventricular ejection fraction (LVEF), LV diastolic function, NYHA functional class and outcome in ...patients with congestive heart failure (CHF), although a substantial number of patients respond poorly to CRT. We investigated whether myocardial collagen metabolism of patients with CHF is implicated in good or poor response to CRT.
Methods
We analyzed collagen synthesis and degradation by measuring the concentrations of aminoterminal propeptides of type I and type III collagen (PINP and PIIINP, resp.) and carboxyterminal telopeptide of type I collagen (ICTP), respectively, in serum of 64 patients with CHF before and 6 months after start of CRT. Patients had NYHA class III–IV, LVEF ≤35%, and QRS duration >120 ms.
Results
In 46 patients, CRT resulted in >10% reduction of LV end-systolic volume (LVESV), referred to as responders, whereas in 18 patients LVESV did not change upon CRT or even increased, referred to as non-responders. Responders demonstrated an increase of serum PINP and PIIINP upon CRT, from 32.9±2.2 to 46.7±4.0 μg/L (p<0.001) and from 4.59±0.24 to 5.13±0.36 μg/L (p<0.05), respectively, whereas serum PINP and PIIINP of non-responders did not change upon CRT (from 41.8±4.3 to 43.8±6.2 μg/L and from 4.03±0.45 to 4.28±0.31 μg/L, resp.). Responders had higher serum levels of ICTP at baseline and at 6 months follow-up (from 3.38±0.54 to 3.12±0.48 μg/L) than non-responders at both time points (from 1.96±0.37 to 1.92±0.38 μg/L), although these differences were not statistically significant.
Conclusion
Compared to future non-responders to CRT, future responders demonstrate relatively low levels of markers of collagen synthesis and relatively high levels of markers of collagen degradation at baseline. Unlike non-responders, responders show an increase in collagen synthesis in the first 6 months of CRT.
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