Persistently high cardiac troponin T (cTnT) levels reflect myocardial damage in heart failure (HF). The presence and extent of myocardial fibrosis assessed by cardiac magnetic resonance (CMR) and high levels of cTnT predict poor prognosis in various cardiomyopathies. However, the association between myocardial fibrosis and transcardiac cTnT release has not been evaluated. This study investigated the correlation between myocardial fibrosis and transcardiac cTnT release from nonischemic failing myocardium. Serum cTnT levels were measured in aortic root (Ao) and coronary sinus (CS) using highly sensitive assay (detection limit >5 ng/L) in 74 nonischemic patients with HF who underwent CMR. Transcardiac cTnT release (ΔcTnT [CS-Ao]) represented the difference between CS and Ao-cTnT levels. Myocardial fibrosis was quantified by late gadolinium enhancement (LGE) volume and %LGE on CMR. cTnT was detectable in 65 patients (88%), and ΔcTnT (CS-Ao) levels were available (ΔcTnT [CS-Ao] >0 ng/L) in 60 patients (81%). LGE was observed in 42 patients (57%), and ΔcTnT (CS-Ao) levels were available in 41 LGE-positive patients (98%). In patients with available cTnT release, ΔcTnT (CS-Ao) levels were significantly higher in LGE-positive patients than those in LGE-negative patients (4.3 [2.2-5.5] vs 1.5 [0.9-2.6] ng/L; p = 0.001). Log (ΔcTnT [CS-Ao]) levels were correlated with LGE volume (r = 0.460, p = 0.003) and %LGE (r = 0.356, p = 0.03). In conclusion, the amount of transcardiac cTnT release was higher in LGE-positive patients than LGE-negative patients and correlated with the extent of LGE in nonischemic patients with HF. These results suggested that ongoing myocardial damage correlates with the presence and extent of myocardial fibrosis.

Background. The pharmacological advantage of combination of an angiotensin receptor blocker (ARB) and a calcium-channel blocker (CCB) is not fully defined. Thi

In the development of atherosclerosis, inflammatory cells adhere to and migrate into the vascular walls by interacting with vascular smooth muscle cells. To investigate the mechanism of aspirin's anti‐atherogenic activity, we examined whether aspirin inhibits the adhesion of lymphocytes to human aortic smooth muscle cells (AoSMC). Aspirin inhibited T‐cell adhesion to AoSMC activated by interleukin 1β (IL‐1β) in a dose‐dependent manner. Antibodies to the adhesion molecules ICAM‐1 or VCAM‐1, but not to E‐selectin, prevented T‐cell adhesion. ICAM‐1 and VCAM‐1 expression stimulated by IL‐1β was reduced by the treatment with aspirin, whereas the expression of E‐selectin was unaffected. Nuclear factor κB (NF‐κB) activity was enhanced by IL‐1β and reduced by aspirin, indicating that decreased ICAM‐1 and VCAM‐1 expression was due to reduced NF‐κB activity.Thus, aspirin inhibits the adhesion of Jurkat T cells to IL‐1β‐activated AoSMC by reducing NF‐κB activity and decreasing expression of ICAM‐1 and VCAM‐1, and may prevent the development of atherosclerosis.

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A growing body of evidence has shown that Fas-mediated apoptosis is involved in atherosclerosis progression. Recent studies have revealed that a single nucleotide polymorphism (SNP) in the Fas promoter region (−670G/A) influences Fas expression. Here, we investigated whether −670G/A SNP influences the incidence of myocardial infarction (MI) by examining a comparison between MI patients (n=154) and control subjects (n=462) in a Japanese population. The allele frequency in each group was A 53.6% /G 46.4% in the MI patients, and A 43.9% /G 56.1% in the non-MI subjects (χ²=8.6; P=0.003). The odds ratio was 2.62 (95% CI: 1.43–4.88). As subjects with the −670AA genotype had a signal transducer and activator of transcription 1 (STAT1)-binding site in the Fas promoter region, STAT-1 activation by interferon-γ may upregulate Fas expression in human vascular smooth muscle cells (VSMCs) of −670AA genotype subjects as described earlier. The Fas upregulation induces excess apoptosis to VSMCs, which leads to unstable plaque formation in atherosclerotic lesions and then potentially to plaque rupture, which can cause MI. Further investigation of hypertensive subjects revealed that the −670AA genotype does not induce hypertension occurrence, supporting that this difference of MI occurrence between the −670AA genotype and the −670GG genotype may be because of plaque rupture followed by excess apoptosis of VSMCs in the atherosclerotic lesion. We conclude that the Fas promoter gene, SNP (−670G/A), may be a risk factor of MI occurrence.