Lectin Pathway of Complement Activation Is Associated with Vulnerability of Atherosclerotic Plaques

Abstract

Inflammatory mechanisms may be involved in atherosclerotic plaque rupture. By using a novel histology-based method to quantify plaque instability here, we assess whether lectin pathway (LP) of complement activation, a major inflammation arm, could represent an index of plaque instability. Plaques from 42 consecutive patients undergoing carotid endarterectomy were stained with hematoxylin-eosin and the lipid core, cholesterol clefts, hemorrhagic content, thickness of tunica media, and intima, including or not infiltration of cellular debris and cholesterol, were determined. The presence of ficolin-1, -2, and -3 and mannose-binding lectin (MBL), LP initiators, was assessed in the plaques by immunofluorescence and in plasma by ELISA. LP activation was assessed in plasma by functional in vitro assays. Patients presenting low stenosis (≤75%) had higher hemorrhagic content than those with high stenosis (>75%), indicating increased erosion. Increased hemorrhagic content and tunica media thickness, as well as decreased lipid core and infiltrated content were associated with vulnerable plaques and therefore used to establish a plaque vulnerability score that allowed to classify patients according to plaque vulnerability. Ficolins and MBL were found both in plaques’ necrotic core and tunica media. Patients with vulnerable plaques showed decreased plasma levels and intraplaque deposition of ficolin-2. Symptomatic patients experiencing a transient ischemic attack had lower plasma levels of ficolin-1. We show that the LP initiators are present within the plaques and their circulating levels change in atherosclerotic patients. In particular, we show that decreased ficolin-2 levels are associated with rupture-prone vulnerable plaques, indicating its potential use as marker for cardiovascular risk assessment in atherosclerotic patients.

Specific contribution of mannose-binding lectin murine isoforms to brain ischemia/reperfusion injury

“…5b). The in vitro assay using acBSA-coated plates, which measures LP activation through ficolins, 18 did not show any difference among the genotypes (Fig. 5c).…”

“…We tested the activation of the LP in mouse plasma (pools from mice belonging to the same experimental group) using an in vitro assay 17 with mannan-coated plates, which measures LP activation through MBL. 18 There was no LP activation in MBL −/− and MBL-A −/− ischemic mice, whereas the LP remained active in Fig. 1 Neuroscore and ischemic volume after 48 h of reperfusion in MBL −/− , MBL-A −/− , and MBL-C −/− mice.…”

The role of the complement factor B‒arginase‒polyamine molecular axis in uremia‐induced cardiac remodeling in mice

“…Hertle et al raised a conclusion from a large-sample cohort that the excessive AP activation would promote poor cardiovascular outcomes [5]. Fumaqalli et al found high expressions of Ficolins and mannose-binding lectin in plaques' necrotic core and tunica media of patients with severe coronary heart disease [6]. Therefore, determination of the exact role of each complement pathway and corresponding components in a specific heart disease will be much helpful to deeply understand the mechanisms of the diseases and provide valid and targeted therapeutic intervention to particular patients.…”

Influência do tratamento da doença periodontal na sirtuína 1 e na lectina ligadora de manose em indivíduos com doença arterial coronária

“…Já o Rugonfalvi-Kiss et al64 observaram que em 123 pacientes que foram submetidos a endarterectomia de carótida e foram acompanhados por eco-dopplergrafia de carótidas, a recorrência de estenose teve associação com altas concentrações de MBL no soro. Berger et al65 estudando pacientes com transplante simultâneo de pâncreas e rim demonstraram que há associação dos níveis de MBL > 400 ng/mL com pior sobrevida do enxerto e levantaram a hipótese de que a MBL contribui para a patogênese da lesão vascular induzida por inflamação, tanto nos vasos dos órgãos transplantados como nos vasos do indivíduo receptor.Assim, é provável que a MBL possua um duplo papel na DAC podendo promover e proteger contra inflamação, dependendo do cenário fisiopatológico no interior da parede do vaso e de que um equilíbrio bem ajustado é o que determina se o complemento é uma vantagem ou desvantagem na DAC 66. 1.3.…”

“…Os autores analisaram as placas de ateroma e as categorizaram pelas características morfológicas associadas à instabilidade da placa 147 , tais como: conteúdo hemorrágico e de colesterol, a área de núcleo lipídico, espessura total da túnica e conteúdo infiltrativo vascular. Eles mostraram a presença da MBL no núcleo necrótico e na camada média da túnica contribuindo para a instabilidade da placa de ateroma 66. Portanto, os níveis de MBL podem ser possíveis sinalizadores de instabilidade da placa aterosclerótica.…”