Expression of monocyte chemoattractant protein-1 in idiopathic dilated cardiomyopathy

Immunological factors have been involved in the pathogenesis of dilated cardiomyopathy (DCM). The cytotoxic action of macrophages is one of the main factors causing cardiac myocyte damage. Monocyte chemoattractant protein-1 (MCP-1) is a major signal for the accumulation of monocytes/macrophages. We examined whether MCP-1 was expressed in the myocardium of DCM patients and whether the expression level was correlated with the degree of impairment of cardiac function. The expression of MCP-1 in the myocardium was determined by immunohistochemistry in endomyocardial biopsy samples from 13 patients. The expression of MCP-1 was found in all myocardial samples from DCM patients but not in those from control subjects. Positive staining for MCP-1 was distinct in cardiac myocytes, interstitium and infiltrating cells. Semi-quantitative analysis revealed that the expression of MCP-1 was inversely correlated with left ventricular ejection fraction. In conclusion, the expression level of MCP-1 in the myocardium was correlated with the degree of impairment of cardiac function in patients with DCM.</p

A 5‐year survivor of endarterectomy for sclerosing undifferentiated intimal sarcoma of the pulmonary artery: Importance of clinical suspicion and careful histologic evaluation

Abstract We present a diagnostically challenging case of intimal sarcoma of the pulmonary artery (PA) due to the histologic finding of a sclerosing appearance with no appreciable spindle/pleomorphic cell proliferation. Initial endarterectomy specimens were composed of sclerosing extracellular matrix with a few bland cells, some recanalization, and fibrin thrombi, impeding the confirmation of intimal sarcoma as these findings were also consistent with chronic thromboembolic pulmonary hypertension. However, the patient experienced recurrence 5 years later, and the second endarterectomy specimens revealed more firm and solid mass and the proliferation of atypical spindle/pleomorphic cells within a myxomatous matrix in the distal PA, leading to the definitive diagnosis of undifferentiated intimal sarcoma of the PA. The archival specimens from the endarterectomy confirmed intense MDM2 expression by immunohistochemistry, suggesting its role as a potential diagnostic marker for intimal sarcoma. This case highlights that prominent sclerosing extracellular matrix with very few atypical cells should raise the possibility of intimal sarcoma of the PA and that high index of suspicion, generous sampling, and ancillary tests are critical for accurate diagnosis. In this case, the tumor was incidentally removed by endarterectomy, resulting in 5 years of survival

Peripartum Serial Echocardiographic Findings in a Patient with Life-threatening Peripartum Cardiomyopathy

A 35-year-old woman was referred to our hospital for the management of acutely decompensated heart failure due to peripartum cardiomyopathy (PPCM). Generally, cardiac examinations are performed after the manifestation of heart failure in patients with PPCM. Thus, reports of serial cardiac examinations before the onset of PPCM are scarce. In this case, we were able to document the serial echocardiographic findings before the onset of life-threatening PPCM. We found that the left ventricular systolic function was preserved at 35 weeks of gestation but declined acutely after delivery at 38 weeks. Although speculative, these findings suggest that left ventricular dilation might precede the onset of PPCM

Transient expression of cellular retinol-binding protein-1 during cardiac repair after myocardial infarction

Retinoic acid (RA) is a vitamin A derivative that exerts pleiotropic biological effects. Intracellular transport and metabolism of RA are regulated by cellular retinol-binding proteins (CRBP). CRBP-1 is transiently expressed in granulation tissue fibroblasts during wound healing; however, its role in cardiac remodeling remains unknown. A rat myocardial infarction (MI) model was established by ligation of the left coronary artery, and hearts were obtained at 3, 6, 15, 30 and 45 days after operation. Heart sections were examined immunohistochemically using anti-vimentin, anti-α-smooth muscle actin (α-SMA), anti-matrix metalloproteinase (MMP)-2, anti-MMP-9 and anti-CRBP-1 antibodies. Infarction involved 48.8 ± 3.6% of the left ventricle and was followed by an important cardiac remodeling. Vimentin-positive fibroblastic cells including α-SMA-positive myofibroblasts expressed CRBP-1 at 3-, 6-, and 15-days after MI. Expression of CRBP-1 reached a maximum at 6-days after infarction. Thereafter, CRBP-1 expression was dramatically decreased, showing a similar tendency to MMP expression. Human heart specimens of individuals with a recent myocardial infarction demonstrated presence of CRBP-1-positive fibroblasts by immunohistochemistry. We have demonstrated that CRBP-1 is transiently expressed by fibroblasts during cardiac remodeling. Our results suggest that CRBP-1 plays a role in ventricular remodeling after MI allegedly through its RA binding activity

Transthyretin derived amyloid deposits in the atrium and the aortic valve: insights from multimodality evaluations and mid-term follow up

Abstract Background Recent studies have reported atrial involvement and coexistence of aortic stenosis in transthyretin (ATTR) cardiac amyloidosis (CA). However, pathological reports of extraventricular ATTR amyloid deposits in atrial structures or heart valves are limited, and the clinical implications of ATTR amyloid deposits outside the ventricles are not fully elucidated. Case presentation We report 3 cases of extraventricular ATTR amyloid deposits confirmed in surgically resected aortic valves and left atrial structures, all of which were unlikely to have significant ATTR amyloidosis infiltrating the ventricles as determined by multimodality evaluation including 99mtechnetium-pyrophosphate scintigraphy, cardiac magnetic resonance, endomyocardial biopsy and their mid-term clinical course up to 5 years. These findings suggested that these were extraventricular ATTR amyloid deposits localized in the aortic valve and the left atrium. Conclusions While long-term observation is required to fully clarify whether these extraventricular ATTR amyloid deposits are truly localized outside the ventricles or are early stages of ATTR-CA infiltrating the ventricles, our 3 cases with multimodality evaluations and mid-term follow up suggest the existence of extraventricular ATTR amyloid deposits localized in the aortic valve and left atrial structures

Molecular genetic characterization of SMAD signaling molecules in pulmonary arterial hypertension

Heterozygous germline mutations of BMPR2 contribute to familial clustering of pulmonary arterial hypertension (PAH). To further explore the genetic basis of PAH in isolated cases, we undertook a candidate gene analysis to identify potentially deleterious variation. Members of the bone morphogenetic protein (BMP) pathway, namely SMAD1, SMAD4, SMAD5, and SMAD9, were screened by direct sequencing for gene defects. Four variants were identified in SMADs 1, 4, and 9 among a cohort of 324 PAH cases, each not detected in a substantial control population. Of three amino acid substitutions identified, two demonstrated reduced signaling activity in vitro. A putative splice site mutation in SMAD4 resulted in moderate transcript loss due to compromised splicing efficiency. These results demonstrate the role of BMPR2 mutation in the pathogenesis of PAH and indicate that variation within the SMAD family represents an infrequent cause of the disease