Prognostic Impacts of Plasma Levels of Cyclophilin A in Patients With Coronary Artery Disease

Ohtsuki, Tomohiro; Satoh, Kimio; Omura, Junichi; Kikuchi, Nobuhiro; Satoh, Taijyu; Kurosawa, Ryo; Nogi, Masamichi; Sunamura, Shinichiro; Yaoita, Nobuhiro; Aoki, Tatsuo; Tatebe, Shunsuke; Sugimura, Koichiro; Takahashi, Jun; Miyata, Satoshi; Shimokawa, Hiroaki

doi:10.1161/atvbaha.116.308986

Cited by 42 publications

(34 citation statements)

References 57 publications

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“…Accordingly, we propose that the anti-inflammatory and anti-oxidative activities of SP-8356 reported by our group [19,21] are associated with reduction of the CypA level in atheroaclerotic plaques. Recently, elevated CypA levels were reported to have a prognostic impact on all-cause death, coronary revascularization and rehospitalization of patients with coronary artery disease [42]. Furthermore, CypA offers superior prognostic value to other conventional biomarkers, such as high-sensitivity C-reactive protein and brain natriuretic peptide [42].…”

Section: Discussionmentioning

confidence: 99%

“…Recently, elevated CypA levels were reported to have a prognostic impact on all-cause death, coronary revascularization and rehospitalization of patients with coronary artery disease [42]. Furthermore, CypA offers superior prognostic value to other conventional biomarkers, such as high-sensitivity C-reactive protein and brain natriuretic peptide [42]. The collective findings support that the feasibility of utilizing the CypA level as a prognostic biomarker and its reduction by inhibitors, such as SP-8356, leading to prognostic improvements in patients with atherosclerosis-related clinical events.…”

Section: Discussionmentioning

confidence: 99%

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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

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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.

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Section: Discussionmentioning

confidence: 99%

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

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“…17 Recently, it was examined whether plasma CyPA levels could predict long-term prognosis of patients with CAD, and the incidence of all-cause death, rehospitalization, and revascularization was higher in patients with higher plasma CyPA levels than in those with lower levels. 31 In particular, plasma CyPA levels had a strong prognostic impact for future revascularization. 31 Plasma CyPA level is a biomarker that exactly reflects the severity of developing arteriosclerosis.…”

Section: Atherosclerosis and Coronary Artery Diseasementioning

confidence: 99%

“…31 In particular, plasma CyPA levels had a strong prognostic impact for future revascularization. 31 Plasma CyPA level is a biomarker that exactly reflects the severity of developing arteriosclerosis. 39 Thus, agents that inhibit CyPA secretion may suppress the development of atherosclerosis in future (Figure 1).…”

Section: Atherosclerosis and Coronary Artery Diseasementioning

confidence: 99%

“…[18][19][20] During the past 15 years, I have focused on a series of studies to elucidate the precise mechanism by which oxidative stress damages vascular function and promotes cardiovascular diseases. 16,21- 31 In 2017, I received the Sato memorial award from the Japanese Circulation Society for these achievements and here, I review my 15 years' work, during which I carried out basic cardiovascular research and clinical application projects. In 2002, I started basic research on the pathogenesis of pulmonary hypertension (PH) as a degree research project, expanded the research area to arteriosclerosis and heart failure (HF) during a stay in the USA, and, since returning to Japan, I have been devoted to translational research accomplished through basic research.…”

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confidence: 99%

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Development of Novel Therapies for Cardiovascular Diseases by Clinical Application of Basic Research

Satoh

2017

Circ J

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Cyclophilin A (CyPA) is secreted from vascular smooth muscle cells, inflammatory cells, activated platelets, and cardiac fibroblasts in response to oxidative stress. Excessive and continuous activation of the RhoA/Rho-kinase system promotes the secretion of CyPA, resulting in the development of multiple cardiovascular diseases. Basigin (Bsg), a transmembrane glycoprotein that activates matrix metalloproteinases, is an extracellular receptor for CyPA that promotes cell proliferation and inflammation. Thus, the CyPA/Bsg system is potentially a novel therapeutic target for cardiovascular diseases. Importantly, plasma CyPA levels are increased in patients with coronary artery disease, abdominal aortic aneurysms, pulmonary hypertension, and heart failure. Moreover, plasma CyPA levels can predict all-cause death in patients with coronary artery disease and pulmonary hypertension. Additionally, plasma soluble Bsg levels are increased and predict all-cause death in patients with heart failure, suggesting that CyPA and Bsg are novel biomarkers for cardiovascular diseases. To discover further novel molecules targeting the CyPA/Bsg system, high-throughput screening of compounds found molecules that ameliorate the development of cardiovascular diseases. In addition to CyPA and Bsg, novel therapeutic targets and their inhibitors for patients with pulmonary arterial hypertension have been recently screened and identified. Ultimately, the final goal is to develop novel biomarkers and medications that will be useful for improving the prognosis and quality of life in patients with cardiovascular diseases.

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Correlations of Serum Cyclophilin A and Melatonin Concentrations with Hypertension-induced Left Ventricular Hypertrophy

Chen

et al. 2017

Archives of Medical Research

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Prognostic Impacts of Plasma Levels of Cyclophilin A in Patients With Coronary Artery Disease

Cited by 42 publications

References 57 publications

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

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

Development of Novel Therapies for Cardiovascular Diseases by Clinical Application of Basic Research

Correlations of Serum Cyclophilin A and Melatonin Concentrations with Hypertension-induced Left Ventricular Hypertrophy

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