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    Francisco Villarreal

    TitleAdjunct Professor
    SchoolUniversity of California, San Diego
    DepartmentMedicine
    Address9500 Gilman Drive #0613-J
    CA La Jolla 92093
    Phone858-534-3630
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      Collapse Research 
      Collapse Research Activities and Funding
      Epicatechin Treatment for Sarcopenia
      NIH/NIA R56AG052593Sep 30, 2017 - Aug 31, 2018
      Role: Principal Investigator
      Epicatechin treatment for sarcopenia
      NIH/NIA R21AG047326Sep 15, 2015 - Aug 31, 2016
      Role: Principal Investigator
      Epicatechin and derivatives to preserve muscle structure function in diabetes
      NIH/NIDDK R01DK098717Mar 10, 2014 - Dec 31, 2017
      Role: Principal Investigator
      Early Phase Pre-Clinical and Initial Clinical Research on Epicatechin
      NIH/NCCIH R01AT008310Sep 1, 2013 - Aug 31, 2014
      Role: Principal Investigator
      Targeting cellular bioenergetics for the prevention and treatment of diabetes
      NIH/NIDDK R24DK092154Aug 1, 2011 - Jul 31, 2013
      Role: Principal Investigator
      Effects of Cocoa Flavonols on Myocardial Infarction Size and Post-Injury Injury
      NIH/NCCIH R21AT004277Sep 30, 2008 - Jul 31, 2011
      Role: Principal Investigator
      26th Annual Meeting of the North Am. Section of the ISHR
      NIH/NHLBI R13HL078318Jul 1, 2004 - Jun 30, 2005
      Role: Principal Investigator
      San Diego IRACDA: Professors for the Future
      NIH/NIGMS K12GM068524Aug 1, 2003 - Jun 30, 2021
      Role: Principal Investigator
      Adenosine Mediated Modulation of Cardiac Fibrosis
      NIH/NHLBI R01HL067922Jul 15, 2002 - Jun 30, 2008
      Role: Principal Investigator
      HEART FIBROBLAST AND COLLAGEN TYPE III REGULATION
      NIH/NHLBI K14HL003160Jul 1, 1994 - Jun 30, 2000
      Role: Principal Investigator
      Molecular biology and mechanics of the cardiac interstitium
      NIH/NHLBI R01HL043617Jul 1, 1989 - Mar 31, 2013
      Role: Principal Investigator

      Collapse Bibliographic 
      Collapse Publications
      Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help.
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      1. Estrada-Mena FJ, Rodriguez A, Mendoza-Lorenzo P, Neri-Gomez T, Manjarrez-Gutierrez G, Perez-Ortiz AC, Ordonez-Razo R, Ceballos G, Villarreal F, Ramirez-Sanchez I. Effects of (-)-epicatechin on frontal cortex DAPC and dysbindin of the mdx mice. Neurosci Lett. 2017 Aug 31; 658:142-149. PMID: 28855126.
        View in: PubMed
      2. Formentini L, Ryan AJ, Gálvez-Santisteban M, Carter L, Taub P, Lapek JD, Gonzalez DJ, Villarreal F, Ciaraldi TP, Cuezva JM, Henry RR. Mitochondrial H+-ATP synthase in human skeletal muscle: contribution to dyslipidaemia and insulin resistance. Diabetologia. 2017 Aug 02. PMID: 28770317.
        View in: PubMed
      3. Varela CE, Rodriguez A, Romero-Valdovinos M, Mendoza-Lorenzo P, Mansour C, Ceballos G, Villarreal F, Ramirez-Sanchez I. Browning effects of (-)-epicatechin on adipocytes and white adipose tissue. Eur J Pharmacol. 2017 Sep 15; 811:48-59. PMID: 28576408.
        View in: PubMed
      4. Beltrán-Partida E, Valdéz-Salas B, Moreno-Ulloa A, Escamilla A, Curiel MA, Rosales-Ibáñez R, Villarreal F, Bastidas DM, Bastidas JM. Improved in vitro angiogenic behavior on anodized titanium dioxide nanotubes. J Nanobiotechnology. 2017 Jan 31; 15(1):10. PMID: 28143540.
        View in: PubMed
      5. Gutiérrez-Salmeán G, Meaney E, Lanaspa MA, Cicerchi C, Johnson RJ, Dugar S, Taub P, Ramírez-Sánchez I, Villarreal F, Schreiner G, Ceballos G. A randomized, placebo-controlled, double-blind study on the effects of (-)-epicatechin on the triglyceride/HDLc ratio and cardiometabolic profile of subjects with hypertriglyceridemia: Unique in vitro effects. Int J Cardiol. 2016 Nov 15; 223:500-506. PMID: 27552564.
        View in: PubMed
      6. Taub PR, Ramirez-Sanchez I, Patel M, Higginbotham E, Moreno-Ulloa A, Román-Pintos LM, Phillips P, Perkins G, Ceballos G, Villarreal F. Beneficial effects of dark chocolate on exercise capacity in sedentary subjects: underlying mechanisms. A double blind, randomized, placebo controlled trial. Food Funct. 2016 Sep 14; 7(9):3686-93. PMID: 27491778; PMCID: PMC5025384 [Available on 09/14/17].
      7. Ramírez-Sánchez I, Rodríguez A, Moreno-Ulloa A, Ceballos G, Villarreal F. (-)-Epicatechin-induced recovery of mitochondria from simulated diabetes: Potential role of endothelial nitric oxide synthase. Diab Vasc Dis Res. 2016 May; 13(3):201-10. PMID: 26993496.
        View in: PubMed
      8. Varela CE, Fromentin E, Roller M, Villarreal F, Ramirez-Sanchez I. Effects of a natural extract of Aronia Melanocarpa berry on endothelial cell nitric oxide production. J Food Biochem. 2016 Aug; 40(4):404-410. PMID: 27616799.
        View in: PubMed
      9. Moreno-Ulloa A, Mendez-Luna D, Beltran-Partida E, Castillo C, Guevara G, Ramirez-Sanchez I, Correa-Basurto J, Ceballos G, Villarreal F. The effects of (-)-epicatechin on endothelial cells involve the G protein-coupled estrogen receptor (GPER). Pharmacol Res. 2015 Oct; 100:309-20. PMID: 26303816; PMCID: PMC4555879 [Available on 10/01/16].
      10. Beltrán-Partida E, Moreno-Ulloa A, Valdez-Salas B, Velasquillo C, Carrillo M, Escamilla A, Valdez E, Villarreal F. Improved Osteoblast and Chondrocyte Adhesion and Viability by Surface-Modified Ti6Al4V Alloy with Anodized TiO2 Nanotubes Using a Super-Oxidative Solution. Materials (Basel). 2015 Mar 02; 8(3):867-883. PMID: 28787976.
        View in: PubMed
      11. Barnett CF, Moreno-Ulloa A, Shiva S, Ramirez-Sanchez I, Taub PR, Su Y, Ceballos G, Dugar S, Schreiner G, Villarreal F. Pharmacokinetic, partial pharmacodynamic and initial safety analysis of (-)-epicatechin in healthy volunteers. Food Funct. 2015 Mar; 6(3):824-33. PMID: 25598082; PMCID: PMC4357542.
      12. Ramirez-Sanchez I, De los Santos S, Gonzalez-Basurto S, Canto P, Mendoza-Lorenzo P, Palma-Flores C, Ceballos-Reyes G, Villarreal F, Zentella-Dehesa A, Coral-Vazquez R. (-)-Epicatechin improves mitochondrial-related protein levels and ameliorates oxidative stress in dystrophic d-sarcoglycan null mouse striated muscle. FEBS J. 2014 Dec; 281(24):5567-80. PMID: 25284161; PMCID: PMC4262719.
      13. Ortiz-Vilchis P, Yamazaki KG, Rubio-Gayosso I, Ramirez-Sanchez I, Calzada C, Romero-Perez D, Ortiz A, Meaney E, Taub P, Villarreal F, Ceballos G. Co-administration of the flavanol (-)-epicatechin with doxycycline synergistically reduces infarct size in a model of ischemia reperfusion injury by inhibition of mitochondrial swelling. Eur J Pharmacol. 2014 Dec 05; 744:76-82. PMID: 25281837.
        View in: PubMed
      14. DeCoux A, Lindsey ML, Villarreal F, Garcia RA, Schulz R. Myocardial matrix metalloproteinase-2: inside out and upside down. J Mol Cell Cardiol. 2014 Dec; 77:64-72. PMID: 25261607; PMCID: PMC4312173.
      15. Moreno-Ulloa A, Nogueira L, Rodriguez A, Barboza J, Hogan MC, Ceballos G, Villarreal F, Ramirez-Sanchez I. Recovery of Indicators of Mitochondrial Biogenesis, Oxidative Stress, and Aging With (-)-Epicatechin in Senile Mice. J Gerontol A Biol Sci Med Sci. 2015 Nov; 70(11):1370-8. PMID: 25143004; PMCID: PMC4715241 [Available on 11/01/16].
      16. Yamazaki KG, Andreyev AY, Ortiz-Vilchis P, Petrosyan S, Divakaruni AS, Wiley SE, De La Fuente C, Perkins G, Ceballos G, Villarreal F, Murphy AN. Intravenous (-)-epicatechin reduces myocardial ischemic injury by protecting mitochondrial function. Int J Cardiol. 2014 Aug 01; 175(2):297-306. PMID: 24908200; PMCID: PMC4506135.
      17. Spinale FG, Villarreal F. Targeting matrix metalloproteinases in heart disease: lessons from endogenous inhibitors. Biochem Pharmacol. 2014 Jul 01; 90(1):7-15. PMID: 24780447; PMCID: PMC4060262.
      18. Moreno-Ulloa A, Romero-Perez D, Villarreal F, Ceballos G, Ramirez-Sanchez I. Cell membrane mediated (-)-epicatechin effects on upstream endothelial cell signaling: evidence for a surface receptor. Bioorg Med Chem Lett. 2014 Jun 15; 24(12):2749-52. PMID: 24794111; PMCID: PMC4157920.
      19. Gutiérrez-Salmeán G, Ortiz-Vilchis P, Vacaseydel CM, Rubio-Gayosso I, Meaney E, Villarreal F, Ramírez-Sánchez I, Ceballos G. Acute effects of an oral supplement of (-)-epicatechin on postprandial fat and carbohydrate metabolism in normal and overweight subjects. Food Funct. 2014 Mar; 5(3):521-7. PMID: 24458104; PMCID: PMC3947792.
      20. Li AH, Liu PP, Villarreal F, Garcia RA. Dynamic changes in myocardial matrix and relevance to disease: translational perspectives. Circ Res. 2014 Feb 28; 114(5):916-27. PMID: 24577970.
        View in: PubMed
      21. Aguilar H, Fricovsky E, Ihm S, Schimke M, Maya-Ramos L, Aroonsakool N, Ceballos G, Dillmann W, Villarreal F, Ramirez-Sanchez I. Role for high-glucose-induced protein O-GlcNAcylation in stimulating cardiac fibroblast collagen synthesis. Am J Physiol Cell Physiol. 2014 May 01; 306(9):C794-804. PMID: 24553187; PMCID: PMC4010805.
      22. Gutiérrez-Salmeán G, Ortiz-Vilchis P, Vacaseydel CM, Garduño-Siciliano L, Chamorro-Cevallos G, Meaney E, Villafaña S, Villarreal F, Ceballos G, Ramírez-Sánchez I. Effects of (-)-epicatechin on a diet-induced rat model of cardiometabolic risk factors. Eur J Pharmacol. 2014 Apr 05; 728:24-30. PMID: 24491839.
        View in: PubMed
      23. Gutierrez-Salmean G, Ciaraldi TP, Nogueira L, Barboza J, Taub PR, Hogan MC, Henry RR, Meaney E, Villarreal F, Ceballos G, Ramirez-Sanchez I. Effects of (-)-epicatechin on molecular modulators of skeletal muscle growth and differentiation. J Nutr Biochem. 2014 Jan; 25(1):91-4. PMID: 24314870; PMCID: PMC3857584.
      24. Taub PR, Ramirez-Sanchez I, Ciaraldi TP, Gonzalez-Basurto S, Coral-Vazquez R, Perkins G, Hogan M, Maisel AS, Henry RR, Ceballos G, Villarreal F. Perturbations in skeletal muscle sarcomere structure in patients with heart failure and type 2 diabetes: restorative effects of (-)-epicatechin-rich cocoa. Clin Sci (Lond). 2013 Oct; 125(8):383-9. PMID: 23642227.
        View in: PubMed
      25. Moreno-Ulloa A, Cid A, Rubio-Gayosso I, Ceballos G, Villarreal F, Ramirez-Sanchez I. Effects of (-)-epicatechin and derivatives on nitric oxide mediated induction of mitochondrial proteins. Bioorg Med Chem Lett. 2013 Aug 01; 23(15):4441-6. PMID: 23791569; PMCID: PMC3741049.
      26. Ramirez-Sanchez I, Nogueira L, Moreno A, Murphy A, Taub P, Perkins G, Ceballos GM, Hogan M, Malek M, Villarreal F. Stimulatory effects of the flavanol (-)-epicatechin on cardiac angiogenesis: additive effects with exercise. J Cardiovasc Pharmacol. 2012 Nov; 60(5):429-38. PMID: 22833114; PMCID: PMC3496054.
      27. Tanabe K, Tamura Y, Lanaspa MA, Miyazaki M, Suzuki N, Sato W, Maeshima Y, Schreiner GF, Villarreal F, Johnson RJ, Nakagawa T. Epicatechin limits renal injury by mitochondrial protection in cisplatin nephropathy. Am J Physiol Renal Physiol. 2012 Nov 01; 303(9):F1264-74. PMID: 22933302.
        View in: PubMed
      28. Fricovsky ES, Suarez J, Ihm SH, Scott BT, Suarez-Ramirez JA, Banerjee I, Torres-Gonzalez M, Wang H, Ellrott I, Maya-Ramos L, Villarreal F, Dillmann WH. Excess protein O-GlcNAcylation and the progression of diabetic cardiomyopathy. Am J Physiol Regul Integr Comp Physiol. 2012 Oct 01; 303(7):R689-99. PMID: 22874425; PMCID: PMC3469670.
      29. Ramirez-Sanchez I, Aguilar H, Ceballos G, Villarreal F. (-)-Epicatechin-induced calcium independent eNOS activation: roles of HSP90 and AKT. Mol Cell Biochem. 2012 Nov; 370(1-2):141-50. PMID: 22865466; PMCID: PMC3812804.
      30. Yamazaki KG, Ihm SH, Thomas RL, Roth D, Villarreal F. Cell adhesion molecule mediation of myocardial inflammatory responses associated with ventricular pacing. Am J Physiol Heart Circ Physiol. 2012 Apr 01; 302(7):H1387-93. PMID: 22268115; PMCID: PMC3330786.
      31. Ceballos G, Villarreal F. The beneficial vascular effects of cacao flavanols: having your cake and eating it too. J Appl Physiol (1985). 2011 Dec; 111(6):1544-5. PMID: 21998263.
        View in: PubMed
      32. Nogueira L, Ramirez-Sanchez I, Perkins GA, Murphy A, Taub PR, Ceballos G, Villarreal F, Hogan MC, Malek MH. (-)-Epicatechin enhances fatigue resistance and oxidative capacity in mouse muscle. J Physiol. 2011 Sep 15; 589(Pt 18):4615-31. PMID: 21788351; PMCID: PMC3208228.
      33. Yamazaki KG, Villarreal F. Ventricular pacing-induced loss of contractile function and development of epicardial inflammation. Am J Physiol Heart Circ Physiol. 2011 Apr; 300(4):H1282-90. PMID: 21297025; PMCID: PMC3075045.
      34. Ramirez-Sanchez I, Maya L, Ceballos G, Villarreal F. (-)-Epicatechin induces calcium and translocation independent eNOS activation in arterial endothelial cells. Am J Physiol Cell Physiol. 2011 Apr; 300(4):C880-7. PMID: 21209365; PMCID: PMC3074631.
      35. Ramirez-Sanchez I, Maya L, Ceballos G, Villarreal F. Fluorescent detection of (-)-epicatechin in microsamples from cacao seeds and cocoa products: Comparison with Folin-Ciocalteu method. J Food Compost Anal. 2010 Dec 01; 23(8):790-793. PMID: 21297935.
        View in: PubMed
      36. Griffin MO, Ceballos G, Villarreal F. Tetracycline compounds with non-antimicrobial organ protective properties: possible mechanisms of action. Pharmacol Res. 2011 Feb; 63(2):102-7. PMID: 20951211; PMCID: PMC3031662.
      37. Griffin MO, Fricovsky E, Ceballos G, Villarreal F. Tetracyclines: a pleitropic family of compounds with promising therapeutic properties. Review of the literature. Am J Physiol Cell Physiol. 2010 Sep; 299(3):C539-48. PMID: 20592239; PMCID: PMC2944325.
      38. Yamazaki KG, Taub PR, Barraza-Hidalgo M, Rivas MM, Zambon AC, Ceballos G, Villarreal F. Effects of (-)-epicatechin on myocardial infarct size and left ventricular remodeling after permanent coronary occlusion. J Am Coll Cardiol. 2010 Jun 22; 55(25):2869-76. PMID: 20579545; PMCID: PMC2915587.
      39. Ramirez-Sanchez I, Maya L, Ceballos G, Villarreal F. (-)-epicatechin activation of endothelial cell endothelial nitric oxide synthase, nitric oxide, and related signaling pathways. Hypertension. 2010 Jun; 55(6):1398-405. PMID: 20404222; PMCID: PMC2874202.
      40. Maya L, Villarreal F. Diagnostic approaches for diabetic cardiomyopathy and myocardial fibrosis. J Mol Cell Cardiol. 2010 Mar; 48(3):524-9. PMID: 19595694; PMCID: PMC2824060.
      41. Romero-Perez D, Agrawal A, Jacobsen J, Yan Y, Thomas R, Cohen S, Villarreal F. Effects of novel semiselective matrix metalloproteinase inhibitors on ex vivo cardiac structure-function. J Cardiovasc Pharmacol. 2009 Jun; 53(6):452-61. PMID: 19365278; PMCID: PMC2835692.
      42. Villarreal F, Epperson SA, Ramirez-Sanchez I, Yamazaki KG, Brunton LL. Regulation of cardiac fibroblast collagen synthesis by adenosine: roles for Epac and PI3K. Am J Physiol Cell Physiol. 2009 May; 296(5):C1178-84. PMID: 19279233; PMCID: PMC2681376.
      43. Epperson SA, Brunton LL, Ramirez-Sanchez I, Villarreal F. Adenosine receptors and second messenger signaling pathways in rat cardiac fibroblasts. Am J Physiol Cell Physiol. 2009 May; 296(5):C1171-7. PMID: 19244482; PMCID: PMC2681375.
      44. Romero-Perez D, Fricovsky E, Yamasaki KG, Griffin M, Barraza-Hidalgo M, Dillmann W, Villarreal F. Cardiac uptake of minocycline and mechanisms for in vivo cardioprotection. J Am Coll Cardiol. 2008 Sep 23; 52(13):1086-94. PMID: 18848143; PMCID: PMC2572824.
      45. Yamazaki KG, Romero-Perez D, Barraza-Hidalgo M, Cruz M, Rivas M, Cortez-Gomez B, Ceballos G, Villarreal F. Short- and long-term effects of (-)-epicatechin on myocardial ischemia-reperfusion injury. Am J Physiol Heart Circ Physiol. 2008 Aug; 295(2):H761-7. PMID: 18567705; PMCID: PMC2519218.
      46. Ashikaga H, Coppola BA, Yamazaki KG, Villarreal F, Omens JH, Covell JW. Changes in regional myocardial volume during the cardiac cycle: implications for transmural blood flow and cardiac structure. Am J Physiol Heart Circ Physiol. 2008 Aug; 295(2):H610-8. PMID: 18515651; PMCID: PMC2519196.
      47. Agrawal A, Romero-Perez D, Jacobsen JA, Villarreal F, Cohen SM. Zinc-binding groups modulate selective inhibition of MMPs. ChemMedChem. 2008 May; 3(5):812-20. PMID: 18181119; PMCID: PMC2836234.
      48. Go K, Horikawa Y, Garcia R, Villarreal F. Fluorescent method for detection of cleaved collagens using O-phthaldialdehyde (OPA). J Biochem Biophys Methods. 2008 Apr 24; 70(6):878-82. PMID: 17573117; PMCID: PMC2836792.
      49. Garcia RA, Go KV, Villarreal F. Effects of timed administration of doxycycline or methylprednisolone on post-myocardial infarction inflammation and left ventricular remodeling in the rat heart. Mol Cell Biochem. 2007 Jun; 300(1-2):159-69. PMID: 17149544.
        View in: PubMed
      50. Puerta DT, Griffin MO, Lewis JA, Romero-Perez D, Garcia R, Villarreal F, Cohen SM. Heterocyclic zinc-binding groups for use in next-generation matrix metalloproteinase inhibitors: potency, toxicity, and reactivity. J Biol Inorg Chem. 2006 Mar; 11(2):131-8. PMID: 16391944.
        View in: PubMed
      51. Zhou D, Lee HS, Villarreal F, Teng A, Lu E, Reynolds S, Qin C, Smith J, Sung KL. Differential MMP-2 activity of ligament cells under mechanical stretch injury: an in vitro study on human ACL and MCL fibroblasts. J Orthop Res. 2005 Jul; 23(4):949-57. PMID: 16023011.
        View in: PubMed
      52. Griffin MO, Jinno M, Miles LA, Villarreal F. Reduction of myocardial infarct size by doxycycline: a role for plasmin inhibition. Mol Cell Biochem. 2005 Feb; 270(1-2):1-11. PMID: 15792348.
        View in: PubMed
      53. García RA, Pantazatos DP, Gessner CR, Go KV, Woods VL, Villarreal F. Molecular interactions between matrilysin and the matrix metalloproteinase inhibitor doxycycline investigated by deuterium exchange mass spectrometry. Mol Pharmacol. 2005 Apr; 67(4):1128-36. PMID: 15665254.
        View in: PubMed
      54. García RA, Brown KL, Pavelec RS, Go KV, Covell JW, Villarreal F. Abnormal cardiac wall motion and early matrix metalloproteinase activity. Am J Physiol Heart Circ Physiol. 2005 Mar; 288(3):H1080-7. PMID: 15486029.
        View in: PubMed
      55. Villarreal F, Asbun J. Peroxisome proliferator-activated receptors ligands, oxidative stress, and cardiac fibroblast extracellular matrix turnover. Hypertension. 2004 Nov; 44(5):621-2. PMID: 15381678.
        View in: PubMed
      56. Asbun J, Manso AM, Villarreal F. Profibrotic influence of high glucose concentration on cardiac fibroblast functions: effects of losartan and vitamin E. Am J Physiol Heart Circ Physiol. 2005 Jan; 288(1):H227-34. PMID: 15345478.
        View in: PubMed
      57. Chen Y, Epperson S, Makhsudova L, Ito B, Suarez J, Dillmann W, Villarreal F. Functional effects of enhancing or silencing adenosine A2b receptors in cardiac fibroblasts. Am J Physiol Heart Circ Physiol. 2004 Dec; 287(6):H2478-86. PMID: 15284071.
        View in: PubMed
      58. Villarreal F, Omens J, Dillmann W, Risteli J, Nguyen J, Covell J. Early degradation and serum appearance of type I collagen fragments after myocardial infarction. J Mol Cell Cardiol. 2004 Apr; 36(4):597-601. PMID: 15081319.
        View in: PubMed
      59. Garcia RA, Pantazatos D, Villarreal F. Hydrogen/deuterium exchange mass spectrometry for investigating protein-ligand interactions. Assay Drug Dev Technol. 2004 Feb; 2(1):81-91. PMID: 15090213.
        View in: PubMed
      60. Villarreal F, Griffin M, Omens J, Dillmann W, Nguyen J, Covell J. Early short-term treatment with doxycycline modulates postinfarction left ventricular remodeling. Circulation. 2003 Sep 23; 108(12):1487-92. PMID: 12952845.
        View in: PubMed
      61. Villarreal F, Zimmermann S, Makhsudova L, Montag AC, Erion MD, Bullough DA, Ito BR. Modulation of cardiac remodeling by adenosine: in vitro and in vivo effects. Mol Cell Biochem. 2003 Sep; 251(1-2):17-26. PMID: 14575299.
        View in: PubMed