The role of Cavin family proteins in cardiovascular disease

• Project/Area Number: 26670407
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Cardiovascular medicine
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Ueyama Tomomi 京都府立医科大学, 医学(系)研究科(研究院), 客員講師 (80379388)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2016: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: カベオラ / Cavin family / cavin family / シグナル伝達

Outline of Final Research Achievements

PTRF/Cavin-1 deficiency in mice causes loss of caveolae in cardiomyocytes, impaired cardiac function accompanying cardiomyocyte hypertrophy and interstitial fibrosis. MURC deficiency in mice attenuates cardiac hypertrophy induced by α1-adrenergic receptor stimulation and pulmonary hypertension induced by hypoxia. MURC deficiency, on the other hand, exacerbated abdominal aortic aneurysm (AAA) in mice. These results reveals that PTRF/Cavin-1 regulates cardiac function, and that MURC is involved in the development of cardiac hypertrophy, pulmonary hypertension, and AAA.

Research Products

• [Journal Article] Loss of MURC/Cavin-4 induces JNK and MMP-9 activity enhancement in vascular smooth muscle cells and exacerbates abdominal aortic aneurysm (2017)
  • Author(s): 13.Miyagawa K, Ogata T, Ueyama T, Kasahara T, Nakanishi N, Naito D, Taniguchi T, Hamaoka T, Maruyama N, Nishi M, Kimura T, Yamada H, Aoki H, Matoba S
  • Journal Title: Biochem Biophys Res Commun Volume: 487 Issue: 3 Pages: 587-593
  • DOI: 10.1016/j.bbrc.2017.04.096
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] MURC deficiency in smooth muscle attenuates pulmonary hypertension (2016)
  • Author(s): 11.Nakanishi N, Ogata T, Naito D, Miyagawa K, Taniguchi T, Hamaoka T, Maruyama N, Kasahara T, Nishi M, Matoba S, Ueyama T
  • Journal Title: Nat Commun Volume: 7 Issue: 1 Pages: 12417-12417
  • DOI: 10.1038/ncomms12417
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] PTRF/Cavin-1 Deficiency Causes Cardiac Dysfunction Accompanied by Cardiomyocyte Hypertrophy and Cardiac Fibrosis (2016)
  • Author(s): 12.Taniguchi T, Maruyama N, Ogata T, Kasahara T, Nakanishi N, Miyagawa K, Naito D, Hamaoka T, Nishi M, Matoba S, Ueyama T
  • Journal Title: PLoS One Volume: 11 Issue: 9 Pages: e0162513-e0162513
  • DOI: 10.1371/journal.pone.0162513
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] The coiled-coil domain of MURC/cavin-4 is involved in membrane trafficking of caveolin-3 in cardiomyocytes. (2015)
  • Author(s): 8.Naito D, Ogata T, Hamaoka T, Nakanishi N, Miyagawa K, Maruyama N, Kasahara T, Taniguchi T, Nishi M, Matoba S, Ueyama T.
  • Journal Title: Am J Physiol Heart Circ Physiol. Volume: 309 Issue: 12 Pages: H2127-H2136
  • DOI: 10.1152/ajpheart.00446.2015
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Long-Term Overexpression of Hsp70 Does Not Protect against Cardiac Dysfunction and Adverse Remodeling in a MURC Transgenic Mouse Model with Chronic Heart Failure and Atrial Fibrillation. (2015)
  • Author(s): 9.Bernardo BC, Sapra G, Patterson NL, Cemerlang N, Kiriazis H, Ueyama T, Febbraio MA, McMullen JR.
  • Journal Title: PLoS One. Volume: 10 Issue: 12 Pages: e0145173-e0145173
  • DOI: 10.1371/journal.pone.0145173
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] The small molecule BGP-15 protects against heart failure and atrial fibrillation in mice. (2014)
  • Author(s): Sapra G, Tham YK, Cemerlang N, Matsumoto A, Kiriazis H, Bernardo BC, Henstridge DC, Ooi JY, Pretorius L, Boey EJ, Lim L, Sadoshima J, Meikle PJ, Mellet NA, Woodcock EA, Marasco S, Ueyama T, Du XJ, Febbraio MA, McMullen JR.
  • Journal Title: Nat Commun. Volume: 5 Pages: 5705-5705
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] MURC/Cavin-4 facilitates recruitment of ERK to caveolae and concentric cardiac hypertrophy induced by α1-adrenergic receptors. (2014)
  • Author(s): Ogata T, Naito D, Nakanishi N, Hayashi YK, Taniguchi T, Miyagawa K, Hamaoka T, Maruyama N, Matoba S, Ikeda K, Yamada H, Oh H, Ueyama T.
  • Journal Title: Proc Natl Acad Sci U S A. Volume: 111 Pages: 3811-3816
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] MURC/Cavin-4 Deficiency in Smooth Muscle Attenuates Pulmonary Hypertension. (2015)
  • Author(s): 1.Nakanishi N, Ogata T, Hamaoka T, Maruyama N, Kasahara T, Nishi M, Ueyama T.
  • Organizer: American Heart Association Scientific Session 2015
  • Place of Presentation: Orlando, USA
  • Year and Date: 2015-11-07
  • Int'l Joint Research
• [Presentation] MURC/Cavin-4 Regulates Cardiac Function via β-adrenergic Receptor Signaling. (2015)
  • Author(s): 2.Hamaoka T, Ogata T, Naito D, Nakanishi N, Miyagawa K, Maruyama N, Kasahara T, Nishi M, Shirayama T, Ueyama T.
  • Organizer: American Heart Association Scientific Session 2015
  • Place of Presentation: Orlando, USA
  • Year and Date: 2015-11-07
  • Int'l Joint Research
• [Presentation] MURC/Cavin-4 Requires the Coiled-coil Domain for Membrane Trafficking of Caveolin-3 in Cardiomyocytes. (2015)
  • Author(s): 3.Nishi M, Ogata T, Naito D, Hamaoka T, Nakanishi N, Miyagawa K, Maruyama N, Kasahara T, Ueyama T.
  • Organizer: American Heart Association Scientific Session 2015
  • Place of Presentation: Orlando, USA
  • Year and Date: 2015-11-07
  • Int'l Joint Research
• [Presentation] Smooth muscle-specific deletion of MURC/Cavin-4 alleviates pulmonary arterial hypertension. (2014)
  • Author(s): Nakanishi N, Ogata T, Miyagawa K, Hamaoka T, Maruyama N, Kasahara T, Ueyama T.
  • Organizer: American Heart Association Scientific Session 2014
  • Place of Presentation: Chicago, USA
  • Year and Date: 2014-11-15 – 2014-11-19
• [Presentation] PTRF/Cavin-1 knock-out mice develop a progressive cardiomyopathy with ERK1/2 hyperactivation and caveolin-3 reduction. (2014)
  • Author(s): Kasahara T, Ogata T, Maruyama N, Taniguchi T, Hamaoka T, Miyagawa K, Nakanishi N, Ueyama T.
  • Organizer: American Heart Association Scientific Session 2014
  • Place of Presentation: Chicago, USA
  • Year and Date: 2014-11-15 – 2014-11-19
• [Presentation] SDPR/Cavin-2 modulates Akt signaling involved in regulation of hypertrophy and apoptosis in cardiomyocytes. (2014)
  • Author(s): Maruyama N, Ogata T, Nakanishi N, Hamaoka T, Miyagawa K, Kasahara T, Ueyama T.
  • Organizer: American Heart Association Scientific Session 2014
  • Place of Presentation: Chicago, USA
  • Year and Date: 2014-11-15 – 2014-11-19
• [Presentation] MURC/Cavin-4 regulates cardiac function through modulation of caveolin-3 function in β-adrenergic receptor signaling. (2014)
  • Author(s): Hamaoka T, Ogata T, Naito D, Nakanishi N, Miyagawa K, Maruyama N, Kasahara T, Shirayama T, Ueyama T.
  • Organizer: American Heart Association Scientific Session 2014
  • Place of Presentation: Chicago, USA
  • Year and Date: 2014-11-15 – 2014-11-19
• [Presentation] MURC/cavin-4 aggravates abdominal aortic aneurysm with JNK overactivation in vascular smooth muscle cells. (2014)
  • Author(s): Miyagawa K, Ogata T, Nakanishi N, Hamaoka T, Maruyama N, Kasahara T, Ueyama T.
  • Organizer: American Heart Association Scientific Session 2014
  • Place of Presentation: Chicago, USA
  • Year and Date: 2014-11-15 – 2014-11-19
• [Presentation] MURC/Cavin-4 deficiency alleviates pulmonary arterial hypertension. (2014)
  • Author(s): Nakanishi N, Ogata T, Maruyama N, Miyagawa K, Hamaoka T, Ueyama T.
  • Organizer: The 18th International Vascular Biology Meeting.
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2014-04-17 – 2014-04-21
• [Remarks] 京都府立医科大学循環器内科学・腎臓内科学HP
  • URL: http://www.f.kpu-m.ac.jp/k/med2/index.html