Function of CD147 in Atherosclerosis and Atherothrombosis

Wang, Cuiping; Jin, Rong; Zhu, Xiaolei; Yan, Jinchuan; Li, Guohong

doi:10.1007/s12265-015-9608-6

Cited by 54 publications

(54 citation statements)

References 80 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Infiltration of immune-competent cells within coronary lesions has been reported by our group [58] and others [59, 60], thus indicating their contribution to plaque vulnerability [11, 61]. Macrophages are the prototypical cells of innate immunity and they progressively accumulate since the initial stage of plaque formation, ingesting lipids and releasing inflammatory mediators that act orchestrating the local and systemic immunological response [62].…”

Section: Immunological Side Of Atherosclerosis:role Of Immune Cellsmentioning

confidence: 59%

Immune-Inflammatory Activation in Acute Coronary Syndromes: A Look into the Heart of Unstable Coronary Plaque

Cimmino

Loffredo

Morello

et al. 2017

CCR

View full text Add to dashboard Cite

In the last twenty years, our comprehension of the molecular mechanisms involved in the formation, progression and complication of atherosclerotic plaque has advanced significantly and the main role of inflammation and immunity in this phenomenon is now largely accepted. Accumulating evidence highlight the crucial role of different inflammatory and immune cells, such as monocytes and T-lymphocytes, in the pathophysiology of atherosclerotic lesion, particularly in contributing to its com-plications, such as rupture or ulceration. According to the new terminology, “vulnerable plaque” identi-fies an inflamed atherosclerotic lesion that is particularly prone to rupture. Once disrupted, prothrom-botic material is exposed to the flowing blood, thus activating coagulation cascade and platelet aggrega-tion, ultimately leading to acute thrombus formation within the coronary vessel. To date this is the key event underlying the clinical manifestations of acute coronary syndromes (ACS).The degree of vessel occlusion (complete vs. incomplete) and the time of blood flow cessation will define the severity of clinical picture. This phenomenon seems to be the final effect of a complex inter-action between different local and systemic factors, involving the degree of inflammation, type of cells infiltration and the rheological characteristics of blood flow at the site of plaque rupture, thrombogenic substrates within the atherosclerotic lesion and different soluble mediators, already present or acutely released in the circulating blood. This article will review currently available data on the pathophysiology of ACS, emphasizing the immunological and inflammatory aspects of vulnerable plaque. We may pos-tulate that intraplaque antigens and local microenvironment will define the immune-inflammatory re-sponse and cells phenotype, thus determining the severity of clinical manifestations.

show abstract

Section: Immunological Side Of Atherosclerosis:role Of Immune Cellsmentioning

confidence: 59%

Immune-Inflammatory Activation in Acute Coronary Syndromes: A Look into the Heart of Unstable Coronary Plaque

Cimmino

Loffredo

Morello

et al. 2017

CCR

View full text Add to dashboard Cite

show abstract

“…CD147 is a key player in the inflammation process [18,34,35]. Specific inhibition of CD147 with small interfering (si) RNA or monoclonal antibody (mAb) has been shown to exert profound anti-atherosclerotic effects, both in vitro and in vivo, through inhibition of CD147-mediated MMP-9 induction [34,36].…”

Section: Discussionmentioning

confidence: 99%

SP-8356, a Novel Inhibitor of CD147-Cyclophilin A Interactions, Reduces Plaque Progression and Stabilizes Vulnerable Plaques in apoE-Deficient Mice

Pahk

Joung

Song

et al. 2019

IJMS

View full text Add to dashboard Cite

Interactions between CD147 and cyclophilin A (CypA) promote plaque rupture that causes atherosclerosis-related cardiovascular events, such as myocardial infarction and stroke. Here, we investigated whether SP-8356 ((1S,5R)-4-(3,4-dihydroxy-5-methoxystyryl)-6, 6-dimethylbicyclo[3.1.1]hept-3-en-2-one), a novel drug, can exert therapeutic effects against plaque progression and instability through disruption of CD147-CypA interactions in apolipoprotein E-deficient (ApoE KO) mice. Immunocytochemistry and immunoprecipitation analyses were performed to assess the effects of SP-8356 on CD147-CypA interactions. Advanced plaques were induced in ApoE KO mice via partial ligation of the right carotid artery coupled with an atherogenic diet, and SP-8356 (50 mg/kg) orally administrated daily one day after carotid artery ligation for three weeks. The anti-atherosclerotic effect of SP-8356 was assessed using histological and molecular approaches. SP-8356 interfered with CD147-CypA interactions and attenuated matrix metalloproteinase-9 activation. Moreover, SP-8356 induced a decreased in atherosclerotic plaque size in ApoE KO mice and stabilized plaque vulnerability by reducing the necrotic lipid core, suppressing macrophage infiltration, and enhancing fibrous cap thickness through increasing the content of vascular smooth muscle cells. SP-8356 exerts remarkable anti-atherosclerotic effects by suppressing plaque development and improving plaque stability through inhibiting CD147-CypA interactions. Our novel findings support the potential utility of SP-8356 as a therapeutic agent for atherosclerotic plaque.Keywords: atherosclerosis; plaque; plaque vulnerability; cluster of differentiation 147 (CD147); matrix metalloproteinase; matrix metalloproteinase-9 (MMP-9) Int.

show abstract

“…CD147 upregulates MMPs through several signaling pathways, including JAK/STAT, Ras-MEK1-MAPK, and PI3k/Akt signaling pathway, 12,13) thus leading to the instability of the plaque. In the present study, FAK was revealed to play an essential role in MMP9 secretion after CD147 stimulation in macrophages.…”

Section: Discussionmentioning

confidence: 99%

The Role of FAK in the Secretion of MMP9 after CD147 Stimulation in Macrophages

Yang

Guo

et al. 2018

Int. Heart J.

View full text Add to dashboard Cite

SummaryTo investigate whether focal adhesion kinase (FAK) can participate in the secretion of matrix metalloproteinase 9 (MMP9) after CD147 stimulation in THP-1 induced macrophages; thus, to explore the potential treatment perspectives for acute coronary syndrome (ACS).Phorbol-12-myristate-13-acetate (PMA) was used to induce THP-1 cells to differentiate into macrophages. To confirm the peak mRNA and protein expression of FAK and MMP9 after the stimulation of CD147, the macrophages were divided into 5 groups (0, 3, 6, 9, and 12 hours), with 0 hours group as control group. To investigate the role of FAK in the secretion of MMP9, with stimulation of CD147 for 9 hours, FAK inhibitor 14 was used to inhibit FAK Y397 phosphorylation. The mRNA and protein expressions were quantified by qRT-PCR and western blotting, respectively.(1) Relative mRNA expression of FAK and MMP9 were both significantly up-regulated (all P < 0.05) after stimulation of CD147, FAK peaked at 9 hours (3.908 ± 0.106 versus 1, P < 0.05), whereas MMP9 peaked at 6 hours (2.522 ± 0.062 versus 1, P < 0.05). (2) Relative protein expression of FAK, pFAK, and MMP9 were all significantly increased after CD147 stimulation (all P < 0.05), FAK (1.930 ± 0.024 versus 1, P < 0.05) and pFAK (1.737 ± 0.021 versus 1, P < 0.05) peaked at 9 hours, whereas MMP9 peaked at 6 hours (1.527 ± 0.033 versus 1, P < 0.05). (3) CD147 up-regulates FAK, pFAK, and MMP9 mRNA and protein expressions in a dosedependent manner. (4) FAK inhibitor 14 significantly reduced the relative protein expression level of pFAK (0.077 ± 0.012 versus 1, P < 0.05) and MMP9 (0.133 ± 0.012) at 9 hours after CD147 stimulation.The results demonstrated that FAK Y397 phosphorylation was involved in the secretion of MMP9 after CD147 stimulation in macrophages and may play a role in the regulation of ACS.(Int Heart J Advance Publication) Key words: Antigens, Focal adhesion protein-tyrosine kinases, Acute coronary syndrome A cute coronary syndrome (ACS) is one of the leading causes of mortality, 1,2) even if there has been a great improvement in the treatment. The formation of thrombus as the progression of vulnerable plaque is an important cause of acute coronary syndromes. The key features of vulnerable plaques include large necrotic core, thin fibrous cap, and abundant foam cells. 3) Great advances have been made in the signaling pathways involved in the formation of unstable plaques for developing therapeutic methods. However, despite the considerable efforts, the mechanisms underlying the vulnerable plagues remain incompletely understood.The imbalance, which leads to plaque rupture, is between the extracellular matrix (ECM) deposition and matrix destruction. CD147, first identified in tumor cells and also known as extracellular matrix metalloproteinase inducer (EMMPRIN), can induce the production of various matrix metalloproteinases (MMPs). 4) MMPs are a family of zinc-dependent proteinases capable of degrading various structural components of ECM, thus leading to ECM destruction and plaque rupture. 5) Th...

show abstract

Function of CD147 in Atherosclerosis and Atherothrombosis

Cited by 54 publications

References 80 publications

Immune-Inflammatory Activation in Acute Coronary Syndromes: A Look into the Heart of Unstable Coronary Plaque

Immune-Inflammatory Activation in Acute Coronary Syndromes: A Look into the Heart of Unstable Coronary Plaque

SP-8356, a Novel Inhibitor of CD147-Cyclophilin A Interactions, Reduces Plaque Progression and Stabilizes Vulnerable Plaques in apoE-Deficient Mice

The Role of FAK in the Secretion of MMP9 after CD147 Stimulation in Macrophages

Contact Info

Product

Resources

About