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KUWAHARA NaoyaGraduate School of Medicine / Department of MedicineAssistant Professor
Research activity information
■ Award- Mar. 2026 The 90th Annual Scientific Meeting of the Japanese Circulation Society (JCS2026), Young Investigator's Award（Clinical Research）, SVEP1: a Novel Fibroblast-Derived Blood Biomarker Reflecting Cardiac Fibrosis
- Dec. 2025 The 9th JCS Council Forum on Basic Cardiovascular Research (JCS Council-BCVR), Award Session Excellent Award, SVEP1: a novel fibroblast-derived blood biomarker for cardiac fibrosis
- Nov. 2025 神戸大学大学院医学研究科, Excellent Research Paper Award, Kobe University School of Medicine, 2024, ACLY Promotes Cardiac Fibrosis via the Regulation of DNL and Histone Acetylation
- Dec. 2024 The 8th JCS Council Forum on Basic Cardiovascular Research (JCS Council-BCVR), Poster Award, ATP citrate lyase promotes cardiac fibrosis via the regulation of de novo lipogenesis and histone acetylation
- Sep. 2024 神戸大学大学院医学研究科内科学講座 循環器内科学分野, Outstanding Paper Award, 2024, Kobe University School of Medicine, Department of Cardiology Alumni Association, Clinical impact of portal vein pulsatility on the prognosis of hospitalized patients with acute heart failure
- Lead, Apr. 2026, Journal of the American Heart Association, English[Refereed]Scientific journal
- BACKGROUND: ATP citrate lyase (ACLY) is a key enzyme in de novo lipogenesis that generates acetyl-CoA from citrate. Although fatty acids are required for energy production and biomass synthesis in the heart, the regulatory mechanisms of ACLY-mediated de novo lipogenesis in pathological cardiac fibroblasts remain unknown. The aim of this study was to investigate the biological role of ACLY in cardiac remodeling. METHODS: Adeno-associated virus serotype 9-mediated shRNA targeting Acly was intravenously injected into C57BL/6J male mice. The mice were subsequently continuously infused with a mixture of angiotensin II and phenylephrine. Cardiac phenotypes were evaluated via histological staining. Cell proliferation assays, stable isotope tracing with 13C-labeled glucose, and chromatin immunoprecipitation assays were performed using human cardiac fibroblasts. RESULTS: ACLY expression was upregulated in the heart sections of mice treated with angiotensin II/phenylephrine, in particular in fibrotic areas. Masson trichrome staining revealed that Acly gene silencing significantly reduced cardiac fibrosis in these mice. Both siRNA-mediated ACLY knockdown and pharmacological ACLY inhibition suppressed the proliferation and expression of fibrous proteins in cultured human cardiac fibroblasts stimulated with transforming growth factor-β. Mechanistically, ACLY inhibition reduced de novo lipogenesis, limiting the fatty acid supply essential for cellular growth and proliferation. It also decreased H3K9 and H3K27 acetylation, in addition to the presence of acetylated H3K9 and H3K27 at the promoter regions of fibrotic genes. CONCLUSIONS: Our findings demonstrate that ACLY plays an important role in maladaptive cardiac fibrosis. ACLY could be a novel therapeutic target to prevent the development of heart failure.Lead, Ovid Technologies (Wolters Kluwer Health), Jun. 2025, Hypertension, 82(6) (6), 1116 - 1128, English[Refereed]Scientific journal
- Springer Science and Business Media LLC, Apr. 2025, Cardiovascular Diabetology, 24(1) (1), English[Refereed]Scientific journal
- BACKGROUND Heart failure (HF) causes extracardiac organ congestion, including in the hepatic portal system. Reducing venous congestion is essential for HF treatment, but evaluating venous congestion is sometimes difficult in patients with chronic HF. The portal vein (PV) flow pattern can be influenced by right atrial pressure. Ultrasound images of the PV are quite easy to obtain and are reproducible among sonographers. However, the association between PV pulsatility and the condition of HF remains unclear. We hypothesize that PV pulsatility at discharge reflects the condition of HF. AIM To evaluate the usefulness of PV pulsatility as a prognostic marker for hospitalized patients with acute HF. METHODS This observational study was conducted from April 2016 to January 2017 and April 2018 to April 2019 at Shinko Hospital. We enrolled 56 patients with acute HF, and 17 patients without HF served as controls. PV flow velocity was measured by ultrasonography on admission and at discharge. We calculated the PV pulsatility ratio (PVPR) as the ratio of the difference between the peak and minimum velocity to the peak velocity. The primary endpoint was cardiac death and HF re-hospitalization. The observation period was 1 year from the first hospitalization. The Kaplan-Meier method was used to determine the stratified composite event-free rates, and the log-rank test was used for comparisons between groups. RESULTS On admission, the PVPR was significantly higher in patients with acute HF than controls (HF: 0.29 ± 0.20 vs controls: 0.08 ± 0.07, P < 0.01). However, the PVPR was significantly decreased after the improvement in HF (admission: 0.29 ± 0.20 vs discharge: 0.18 ± 0.15, P < 0.01) due to the increase in minimum velocity (admission: 12.6 ± 4.5 vs discharge: 14.6 ± 4.6 cm/s, P = 0.03). To elucidate the association between the PVPR and cardiovascular outcomes, the patients were divided into three groups according to the PVPR tertile at discharge (PVPR-T1: 0 ≤ PVPR ≤ 0.08, PVPR-T2: 0.08 < PVPR ≤ 0.21, PVPR-T3: PVPR > 0.21). The Kaplan-Meier analysis showed that patients with a higher PVPR at discharge had the worst prognosis among the groups. CONCLUSION PVPR at discharge reflects the condition of HF. It is also a novel prognostic marker for hospitalized patients with acute HF.Lead, Baishideng Publishing Group Inc., Nov. 2023, World Journal of Cardiology, 15(11) (11), 599 - 608, English[Refereed]Scientific journal
- 2024, 日本循環器学会学術集会(Web), 88thHypercholesterolemia with Heterozygous Pathogenic Mutations in ABCG5 Genes
- 2024, 日本動脈硬化学会総会・学術集会プログラム・抄録集(Web), 56thEffectiveness of ezetimibe and colestimide against hypercholesterolemia associated with heterozygous mutations of ABCG5 or 8
- The 90th Annual Scientific Meeting of the Japanese Circulation Society (JCS2026) Young Investigator's Award (Clinical Research), Mar. 2026, EnglishSVEP1: a Novel Fibroblast Derived Blood Biomarker Reflecting Cardiac FibrosisOral presentation
- The 90th Annual Scientific Meeting of the Japanese Circulation Society (JCS2026) Oral Presentation (Heart Failure 2), Mar. 2026, EnglishSVEP1: a fibroblast derived novel and specific circulating biomarker for cardiac fibrosisOral presentation
- The 9th JCS Council Forum on Basic Cardiovascular Research (JCS Council-BCVR) Award Session, Dec. 2025, EnglishSVEP1: A Novel fibroblast-derived blood biomarker for early cardiac fibrosisOral presentation
- American Heart Association Scientific Sessions, Nov. 2025, EnglishThe inhibition of ATP citrate lyase prevents pathological cardiac fibrosis via the regulation of de novo lipogenesis and histone acetylationOral presentation
- XXV World Congress International Society for Heart Research (ISHR2025 NARA), Early Career Symposium, May 2025, EnglishATP citrate lyase promotes pathological cardiac fibrosis via the regulation of de novo lipogenesis and histone acetylation.Poster presentation
- XXV World Congress International Society for Heart Research (ISHR2025 NARA), May 2025, EnglishATP citrate lyase promotes pathological cardiac fibrosis via the regulation of de novo lipogenesis and histone acetylationNominated symposium
- The 89th Annual Scientific Meeting of the Japanese Circulation Society (JCS2025), Mar. 2025, EnglishInhibition of ATP citrate lyase prevents cardiac fibrosis via the regulation of de novo lipogenesis and histone acetylationOral presentation
- American Heart Association Scientific Sessions, 2025, EnglishSVEP1 as a novel biomarker for cardiac fibrosis: Association with CT-derived extracellular volume and functional role in cardiac fibrosisPoster presentation
- The 8th JCS Council Forum on Basic Cardiovascular Research (JCS Council-BCVR), Dec. 2024, EnglishATP citrate lyase promotes cardiac fibrosis via the regulation of de novo lipogenesis and histone acetylationPoster presentation
- The 85th Annual Scientific Meeting of the Japanese Circulation Society (JCS2021), Mar. 2021, EnglishThe clinical impact of portal vein pulsatility on the prognosis of hospitalized acute heart failure patientsPoster presentation
- American Heart Association Scientific Sessions, Nov. 2020, EnglishThe clinical impact of portal vein pulsatility on the prognosis of hospitalized acute heart failure patientsPoster presentation
- American College of Cardiology’s 69th Annual Scientific Sessions, Mar. 2020, EnglishThe impact of portal vein pulsatile on the prognosis of hospitalized acute heart failure patientsPoster presentation
■ Research Themes