Cardiovascular Pathology最新文献

In recent years, there has been an explosive growth of research to decipher the pathobiologic relevance of cell death in the development and progression of various cardiovascular disorders such as arterial remodeling and atherosclerosis. High rates of cell death have been reported in animal models, particularly following balloon catheter injury. Also, in humans there is considerable evidence indicating a close connection between cell death and atherosclerosis. In this regard, diverse biochemical and molecular analysis have suggested that intraplaque cells preferentially die by apoptosis, a mode of cell death considered to be active, highly regulated and programmed. In contrast to apoptosis, necrosis has been classically defined as an uncontrolled form of cell death that can occur in response to chemical or physical insults such as trauma, infection, toxins, or lack of blood supply. Necrosis has long been known to be present within atherosclerotic plaques but to date it is still less well understood and characterized than apoptosis. In addition, although electron microscopy (EM) remains essential in cell death research, only a very small proportion of studies deal with the ultrastructural aspects of cell death and/or include EM images to support their findings. As a consequence, many features of cell death modes in human atherosclerosis have not yet been thoroughly investigated and defined. The present study was undertaken to provide an ultrastructural description of the route/s by which intraplaque cells can die also suggesting novel insights for future research.

The ongoing epidemic caused by the coronavirus SARS-CoV-2 is characterized by a variety of pathologic processes within the syndrome of COVID-19. Usually beginning as an upper respiratory infection with potential progression to a pneumonitis, many cases of COVID-19 that show minimal signs or symptoms initially may develop adverse systemic sequelae later, such as widespread thrombo-embolic phenomena, systemic inflammatory disorders (especially in children), or vasculitis. Here, we present a patient who suffered a sudden cardiac death following persistent SARS-CoV-2 viral positivity for four-and-one-half months after a mild clinical viral course. At routine autopsy, a remarkable plasma cell-rich necrotizing aortitis was uncovered. The aortic intima displayed diffuse, circumferential ongoing chronic intimal edema, inflammation, and neo-vascularization. The plasma cell-rich inflammatory process also involved the origin of the left main coronary artery (LM) causing a coronary arteritis accompanied by subacute, stenosing intimal vascular smooth muscle cell (VSMC) proliferation resulting in acute myocardial necrosis as a cause of death. A similar vasculitis and plaque were noted during the routine autopsy at the ostium of the celiac artery; vasculitis was not found systemically or in smaller caliber vessels. Through a variety of techniques including extensive histopathologic and immunohistochemical characterization, immunostaining localization of viral antigen, and transmission electron microscopy we present highly suggestive evidence that this unique necrotizing, plasma cell-rich aortitis is a rare sequela of COVID-19.

Fenestrations in semilunar valves of human hearts have been incidentally described during autopsies since the 1800s, and were thought to be a degenerative process of the valve cusps. Due to the nature of autopsy, prior literature has primarily examined these fenestrations in pathologic hearts, and has implicated them in leading to valve insufficiency, regurgitation, and cusp rupture. More recent studies have predicted an increase in fenestration prevalence in the rapidly aging United States and have warned of a potential increase in fenestration-related valvular pathology. Herein, we analyze fenestration prevalence in 403 healthy human hearts and report findings that differ from these prior reports, and emphasize that fenestrations may not necessarily portend significant valvular dysfunction.

Introduction

Described for 60 years under various names, the carotid web is a suspected cause of cryptogenic stroke, especially in young patients. The web creates an intraluminal protrusion that may contribute to turbulent flow and thrombus embolization into cerebral arteries. Although the carotid web has frequently been related to arterial fibrodysplasia, its natural history and pathological description remain unclear.

Patients

Among all consecutive patients admitted to the stroke unit of Sainte-Anne Hospital and referred to the vascular surgery department from January 2015 to December 2022, we retrospectively identified 9 patients with a carotid web. The surgical specimens of the 9 patients were submitted to systematic pathological analysis.

Results

The patients with a histologically confirmed carotid web were young (median age was 42 years), prominently women (7/9), and presenting with low cardiovascular risk. Eight patients had a stroke proven by a magnetic resonance imaging, and 1 had transient monocular amaurosis. The typical pathological lesion supporting the imaging pattern of the carotid web was a focal eccentric intimal hyperplasia forming a protruding lesion characterized by a population of vascular smooth muscle cells intermingled in an abundant, most often loose extracellular matrix. Pathologically proven thrombus was observed in 4 cases. Importantly atherosclerosis was absent.

Conclusion

Histological features in our 9 cases strengthen carotid web characterization as a homogeneous pattern of localized intimal hyperplasia. It is a unique entity consistent with intimal fibroplasia, distinct from medial fibromuscular dysplasia and early atherosclerosis.

Background

In coronary atherosclerotic disease, the proliferation of intimal smooth muscle cells (SMCs) is regarded as beneficial with respect to stable and unstable plaques, but is thought detrimental in discussions on coronary stent restenosis. To resolve this discrepancy, we focused on the quality, not quantity, of intimal SMCs in coronary atherosclerotic disease.

Methods

Autopsied coronary artery specimens from seven patients implanted with bare metal stents (BMS), three with paclitaxel-eluting stents (PES), and 10 with sirolimus (rapamycin)-eluting stents (SES) were immunostained for SMC markers. Cultured human coronary artery SMCs were also treated with sirolimus and paclitaxel.

Results

Intimal SMC differentiation, estimated by the ratio of h-caldesmon⁺ cells to α-smooth muscle actin⁺ (α-SMA⁺) cells, was significantly increased whereas dedifferentiation, estimated from the ratio of fibroblast activation protein alpha (FAPα)⁺ cells to α-SMA⁺ cells, was significantly decreased, in tissues of SES compared with BMS cases. No difference in the degree of differentiation was found between PES and BMS cases or between the three groups in nonstented arteries used as controls. Correlation analyses for each field of view revealed a significant positive correlation between h-caldesmon and calponin staining but significant negative correlations with FAPα staining in α-SMA⁺ cells. Cultured SMCs were shorter (dedifferentiated) and showed an increased FAPα/α-SMA protein when treated with paclitaxel, whereas they became elongated (differentiated) and showed increased calponin/α-SMA proteins with sirolimus.

Conclusions

The SMCs of the coronary intima may differentiate after SES implantation. SMC differentiation may explain both the plaque stabilization and reduced risk of reintervention associated with SES.