La galectina-3, una nueva diana terapéutica para las alteraciones cardiovasculares asociadas al desarrollo de la estenosis aórtica severa

Autores/as

  • V. Arrieta
  • J.R. Sádaba
  • V. Álvarez
  • J.A. Rodríguez
  • N. López-Andrés

DOI:

https://doi.org/10.23938/ASSN.0643

Resumen

La estenosis aórtica severa degenerativa (EA) es una enfermedad muy prevalente, cuya incidencia se incrementará en los próximos años debido al envejecimiento de la población. Actualmente no existe ningún tratamiento farmacológico que retarde su progresión y, cuando aparecen los síntomas, la cirugía de recambio valvular es la única opción. La EA se caracteriza por la calcificación de la válvula aórtica y por la aparición de fibrosis miocárdica. Sin embargo, no se conocen los mecanismos fisiopatológicos de la EA necesarios para identificar y desarrollar nuevas estrategias terapéuticas adecuadas. La Galectina-3 (Gal-3) regula funciones biológicas como el crecimiento, la diferenciación, la apoptosis, la inflamación o la fibrosis. Esta revisión resume los principales trabajos que describen el potencial de la Gal-3 como diana terapéutica para las alteraciones cardíacas y valvulares asociadas con el desarrollo de EA.

Palabras clave. Galectina-3. Estenosis aórtica. Fibrosis miocárdica. Calcificación valvular.

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IUNG B, BARON G, BUTCHART EG, DELAHAYE F, GOHLKE-BÄRWOLF C, LEVANG OW et al. A prospective survey of patients with valvular heart disease in Europe: The Euro heart survey on valvular heart disease. Eur Heart J 2003; 24: 1231-1243. https://doi.org/10.1016/S0195-668X(03)00201-X

OʼBRIEN KD. Epidemiology and genetics of calcific aortic valve disease. J Investig Med 2007; 55: 284-291; https://doi.org/10.2310/6650.2007.00010

DANIELSEN R, ASPELUND T, HARRIS TB, GUDNASON V. The prevalence of aortic stenosis in the elderly in Iceland and predictions for the coming decades: the AGES-Reykjavík study. Int J Cardiol 2014; 20: 916-922. https://doi.org/10.1016/j.ijcard.2014.08.053

OTTO CM, BURWASH IG, LEGGET ME, MUNT BI, FUJIOKA M, HEALY NL et al. Prospective study of asymptomatic valvular aortic stenosis. Clinical, echocardiographic, and exercise predictors of outcome. Circulation 1997; 6: 262-2270; https://doi.org/10.1161/01.CIR.95.9.2262

MISFELD M, SIEVERS H-H. Heart valve macro- and microstructure. Philos Trans R Soc Lond B Biol Sci 2007; 29: 1421-1436; https://doi.org/10.1098/rstb.2007.2125

DOEHRING TC, KAHELIN M, VESELY I. Mesostructures of the aortic valve. J Heart Valve Dis 2005; 14: 679-686.

STEPHENS EH, CHU C-K, GRANDE-ALLEN KJ. Valve proteoglycan content and glycosaminoglycan fine structure are unique to microstructure, mechanical load and age: Relevance to an age-specific tissue-engineered heart valve. Acta Biomater 2008; 4: 1148-1160. https://doi.org/10.1016/j.actbio.2008.03.014

HELSKE S, KUPARI M, LINDSTEDt KA, KOVANEN PT. Aortic valve stenosis: an active atheroinflammatory process. Curr Opin Lipidol 2007; 18: 483-491. https://doi.org/10.1097/MOL.0b013e3282a66099

BUTCHER JT, NEREM RM. Valvular endothelial cells and the mechanoregulation of valvular pathology. Philos Trans R Soc B Biol Sci 2007; 29: 1445-1457. https://doi.org/10.1098/rstb.2007.2127

BOSSÉ Y, MIQDAD A, FOURNIER D, PÉPIN A, PIBAROT P, MATHIEU P. Refining molecular pathways leading to calcific aortic valve stenosis by studying gene expression profile of normal and calcified stenotic human aortic valves. Circ Cardiovasc Genet 2009; 2: 489-498. https://doi.org/10.1161/CIRCGENETICS.108.820795

MOHLER ER, GANNON F, REYNOLDS C, ZIMMERMAN R, KEANE MG, KAPLAN FS. Bone formation and inflammation in cardiac valves. Circulation 2001; 20: 1522-1528. https://doi.org/10.1161/01.CIR.103.11.1522

BÄCK M, GASSER TC, MICHEL J-B, CALIGIURI G. Biomechanical factors in the biology of aortic wall and aortic valve diseases. Cardiovasc Res 2013; 15: 232-241. https://doi.org/10.1093/cvr/cvt040

MERRYMAN WD, YOUN I, LUKOFF HD, KRUEGER PM, GUILAK F, HOPKINS RA et al. Correlation between heart valve interstitial cell stiffness and transvalvular pressure: implications for collagen biosynthesis. Am J Physiol Heart Circ Physiol 2006; 290: H224-231. https://doi.org/10.1152/ajpheart.00521.2005

TOWLER DA. Molecular and cellular aspects of calcific aortic valve disease. Circ Res 2013; 5: 198-208. https://doi.org/10.1161/CIRCRESAHA.113.300155

MILLER JD, WEISS RM, SERRANO KM, BROOKS RM, BERRY CJ, ZIMMERMAN K et al. Lowering plasma cholesterol levels halts progression of aortic valve disease in mice. Circulation 2009; 26: 2693-2701. https://doi.org/10.1161/CIRCULATIONAHA.108.834614

VANHOUTTE D, VAN ALMEN GC, VAN AELST LNL, VAN CLEEMPUT J, DROOGNÉ W, JIN Y et al. Matricellular proteins and matrix metalloproteinases mark the inflammatory and fibrotic response in human cardiac allograft rejection. Eur Heart J 2013; 1: 1930-1941. https://doi.org/10.1093/eurheartj/ehs375

POGGIO P, SAINGER R, BRANCHETTI E, GRAU JB, LAI EK, Gorman RC et al. Noggin attenuates the osteogenic activation of human valve interstitial cells in aortic valve sclerosis. Cardiovasc Res 2013; 1: 402-410. https://doi.org/10.1093/cvr/cvt055.

DWECK MR, BOON NA, NEWBY DE. Calcific Aortic Stenosis. J Am Coll Cardiol 2012; 6: 1854-1863. https://doi.org/10.1016/j.jacc.2012.02.093

RAJAMANNAN NM, SUBRAMANIAM M, SPRINGETT M, SEBO TC, NIEKRASZ M, MCCONNELL JP et al. Atorvastatin inhibits hypercholesterolemia-induced cellular proliferation and bone matrix production in the rabbit aortic valve. Circulation 2002; 4: 2660-2665. https://doi.org/10.1161/01.CIR.0000017435.87463.72.

RAJAMANNAN NM, SUBRAMANIAM M, STOCK SR, STONE NJ, SPRINGETT M, IGNATIEV KI et al. Atorvastatin inhibits calcification and enhances nitric oxide synthase production in the hypercholesterolaemic aortic valve. Heart 2005; 1: 806-810. https://doi.org/10.1136/hrt.2003.029785

CHAN KL, TEO K, DUMESNIL JG, NI A, TAM J, Astronomer Investigators. Effect of lipid lowering with rosuvastatin on progression of aortic stenosis: results of the aortic stenosis progression observation: measuring effects of rosuvastatin (ASTRONOMER) trial. Circulation 2010; 19: 306-314. https://doi.org/10.1161/CIRCULATIONAHA.109.900027.

COWELL SJ, NEWBY DE, PRESCOTT RJ, BLOOMFIELD P, REID J, NORTHRIDGE DB et al. A randomized trial of intensive lipid-lowering therapy in calcific aortic stenosis. N Engl J Med 2005; 352: 2389-2397. https://doi.org/10.1056/NEJMoa043876

MANN DL. Left ventricular size and shape: determinants of mechanical signal transduction pathways. Heart Fail Rev 2005; 10: 95-100. https://doi.org/10.1007/s10741-005-4636-y

HEIN S, ARNON E, KOSTIN S, SCHÖNBURG M, ELSÄSSER A, POLYAKOVA V et al. Progression from compensated hypertrophy to failure in the pressure-overloaded human heart: structural deterioration and compensatory mechanisms. Circulation 2003; 107: 984-991. https://doi.org/10.1161/01.CIR.0000051865.66123.B7

DUMIC J, DABELIC S, FLÖGEL M. Galectin-3: an open-ended story. Biochim biophys acta. 2006; 1760: 616-635. https://doi.org/10.1016/j.bbagen.2005.12.020

DENNIS JW, PAWLING J, CHEUNG P, PARTRIDGE E, DEMETRIOU M. UDP-N-acetylglucosamine:alpha-6-D-mannoside beta1,6 N-acetylglucosaminyltransferase V (Mgat5) deficient mice. Biochim Biophys Acta 2002; 19: 414-422. https://doi.org/10.1016/S0304-4165(02)00411-7

OCHIENG J, FURTAK V, LUKYANOV P. Extracellular functions of galectin-3. Glycoconj J 2002; 19: 527-535. https://doi.org/10.1023/B:GLYC.0000014082.99675.2f

KIM H, LEE J, HYUN JW, PARK JW, JOO H, SHIN T. Expression and immunohistochemical localization of galectin-3 in various mouse tissues. Cell Biol Int 2007; 31: 655-662. https://doi.org/10.1016/j.cellbi.2006.11.036

SHARMA UC, POKHAREL S, VAN BRAKEL TJ, VAN BERLO JH, CLEUTJENS JPM, SCHROEN B et al. Galectin-3 marks activated macrophages in failure-prone hypertrophied hearts and contributes to cardiac dysfunction. Circulation 2004; 110: 3121-3128. https://doi.org/10.1161/01.CIR.0000147181.65298.4D

CALVIER L, MIANA M, REBOUL P, CACHOFEIRO V, MARTINEZ-MARTINEZ E, de BOER RA et al. Galectin-3 mediates aldosterone-induced vascular fibrosis. Arterioscler Thromb Vasc Biol 2013; 33: 67-75. https://doi.org/10.1161/ATVBAHA.112.300569

WAN SY, ZHANG TF, DING Y. Galectin-3 enhances proliferation and angiogenesis of endothelial cells differentiated from bone marrow mesenchymal stem cells. Transplant Proc 2011; 43: 3933-3938. https://doi.org/10.1016/j.transproceed.2011.10.050

SÁDABA JR, MARTÍNEZ-MARTÍNEZ E, ARRIETA V, ÁLVAREZ V, FERNÁNDEZ-CELIS A, IBARROLA J et al. Role for galectin-3 in calcific aortic valve stenosis. J Am Heart Assoc 2016; 5. https://doi.org/10.1161/JAHA.116.004360

PAPASPYRIDONOS M, MCNEILL E, DE BONO JP, SMITH A, BURNAND KG, CHANNON KM et al. Galectin-3 is an amplifier of inflammation in atherosclerotic plaque progression through macrophage activation and monocyte chemoattraction. Arterioscler Thromb Vasc Biol 2008; 28: 433-440. https://doi.org/10.1161/ATVBAHA.107.159160

YU L, RUIFROK WPT, MEISSNER M, BOS EM, VAN GOOR H, SANJABI B et al. Genetic and pharmacological inhibition of galectin-3 prevents cardiac remodeling by interfering with myocardial fibrogenesis. Circ Heart Fail 2013; 6: 107-117. https://doi.org/10.1161/CIRCHEARTFAILURE.112.971168

HO MK, SPRINGER TA. Mac-2, a novel 32,000 Mr mouse macrophage subpopulation-specific antigen defined by monoclonal antibodies. J Immunol 1982; 128: 1221-1228.

DE BOER RA, VAN DER VELDE AR, MUELLER C, VAN VELDHUISEN DJ, ANKER SD, PEACOCK WF et al. Galectin-3: A Modifiable risk factor in heart failure. Cardiovasc Drugs Ther 2014; 28: 237-246. https://doi.org/10.1007/s10557-014-6520-2

MARTÍNEZ-MARTÍNEZ E, LÓPEZ-ÁNDRES N, JURADO-LÓPEZ R, ROUSSEAU E, BARTOLOMÉ MV, FERNÁNDEZ-CELIS A et al. Galectin-3 participates in cardiovascular remodeling associated with obesity. Hypertension 2015; 66: 961-969. https://doi.org/10.1161/HYPERTENSIONAHA.115.06032

CHEN X, ZHANG R, ZHANG Q, XU Z, XU F, LI D et al. Microtia patients: Auricular chondrocyte ECM is promoted by CGF through IGF-1 activation of the IGF-1R/PI3K/AKT pathway. J Cell Physiol 2018. https://doi.org/10.1002/jcp.27316

MARKOWSKA AI, JEFFERIES KC, PANJWANI N. Galectin-3 protein modulates cell surface expression and activation of vascular endothelial growth factor receptor 2 in human endothelial cells. J Biol Chem 2011; 25: 29913-29921. https://doi.org/10.1074/jbc.M111.226423

GS AK, RAJ B, SANTHOSH KS, SANJAY G, KARTHA CC. Ascending aortic constriction in rats for creation of pressure overload cardiac hypertrophy model. J Vis Exp 2014; e50983. https://doi.org/10.3791/50983

MOURINO-ALVAREZ L, BALDAN-MARTIN M, GONZALEZ-CALERO L, MARTINEZ-LABORDE C, SASTRE-OLIVA T, MORENO-LUNA R et al. Patients with calcific aortic stenosis exhibit systemic molecular evidence of ischemia, enhanced coagulation, oxidative stress and impaired cholesterol transport. Int J Cardiol 2016; 225: 99-106. https://doi.org/10.1016/j.ijcard.2016.09.089

KADEN JJ, DEMPFLE C-E, GROBHOLZ R, TRAN H-T, KILIÇ R, SARIKOÇ A et al. Interleukin-1 beta promotes matrix metalloproteinase expression and cell proliferation in calcific aortic valve stenosis. Atherosclerosis 2003; 25: 205-211. https://doi.org/10.1016/S0021-9150(03)00284-3

MALEK AM, GIBBONS GH, DZAU VJ, IZUMO S. Fluid shear stress differentially modulates expression of genes encoding basic fibroblast growth factor and platelet-derived growth factor B chain in vascular endothelium. J Clin Invest 1993; 1: 2013-2021. https://doi.org/10.1172/JCI116796

LAURENT S, BOUTOUYRIE P, ASMAR R, GAUTIER I, LALOUX B, GUIZE L et al. Aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in hypertensive patients. Hypertens (Dallas, Tex 1979); 2001; 25: 1236-1241; https://doi.org/10.1161/01.HYP.37.5.1236

GOULD ST, SRIGUNAPALAN S, SIMMONS CA, ANSETH KS. Hemodynamic and cellular response feedback in calcific aortic valve disease. Circ Res 2013; 5: 186-197. https://doi.org/10.1161/CIRCRESAHA.112.300154

AHAMED J, BURG N, YOSHINAGA K, JANCZAK CA, RIFKIN DB, COLLER BS. In vitro and in vivo evidence for shear-induced activation of latent transforming growth factor- 1. Blood 2008; 1: 3650-3660. https://doi.org/10.1182/blood-2008-04-151753

BOBROWSKA B, WIECZOREK-SURDACKA E, KRUSZELNICKA O, CHYRCHEL B, SURDACKI A, DUDEK D. Clinical correlates and prognostic value of plasma galectin-3 levels in degenerative aortic stenosis: a single-center prospective study of patients referred for invasive treatment. Int J Mol Sci 2017; 29: 947. https://doi.org/10.3390/ijms18050947

BÄCK M, GASSER TC, MICHEL J-B, CALIGIURI G. Biomechanical factors in the biology of aortic wall and aortic valve diseases. Cardiovasc Res 2013; 15: 232-241. https://doi.org/10.1093/cvr/cvt040

SÁDABA JR, MARTÍNEZ-MARTÍNEZ E, ARRIETA V, ÁLVAREZ V, FERNÁNDEZ-CELIS A, IBARROLA J et al. Role for galectin-3 in calcific aortic valve stenosis. J Am Heart Assoc 2016; 4. https://doi.org/10.1161/JAHA.116.004360

CIOFFI G, FAGGIANO P, VIZZARDI E, TARANTINI L, CRAMARIUC D, GERDTS E et al. Prognostic effect of inappropriately high left ventricular mass in asymptomatic severe aortic stenosis. Heart 2011; 15: 301-330. https://doi.org/10.1136/hrt.2010.192997

ARRIETA V, MARTINEZ-MARTINEZ E, IBARROLA J, ALVAREZ V, SÁDABA R, GARCIA-PEÑA A et al. A role for galectin-3 in the development of early molecular alterations in short-term aortic stenosis. Clin Sci (Lond) 2017; 1: 935-949. https://doi.org/10.1042/CS20170145

WU CK, SU MY, LEE JK, CHIANG FT, HWANG JJ, LIN JL et al. Galectin-3 level and the severity of cardiac diastolic dysfunction using cellular and animal models and clinical indices. Sci Rep 2015; 5: 17007. https://doi.org/10.1038/srep17007

ZHOU K, ZHOU Y, ZHAO Y, TAN C, YUAN Z, LI J et al. The relationship between galectin-3 and different patterns of ventricular geometry remodelling in aortic valve stenosis. Heart Lung Circ 2016; 25: 371-377. https://doi.org/10.1016/j.hlc.2015.08.021

BALDENHOFER G, ZHANG K, SPETHMANN S, LAULE M, EILERS B, LEONHARDT F et al. Galectin-3 predicts short- and long-term outcome in patients undergoing transcatheter aortic valve implantation (TAVI). Int J Cardiol 2014; 20: 912-917. https://doi.org/10.1016/j.ijcard.2014.10.010

CALVIER L, MARTINEZ-MARTINEZ E, MIANA M, CACHOFEIRO V, ROUSSEAU E, SÁDABA JR et al. The impact of galectin-3 inhibition on aldosterone-induced cardiac and renal injuries. JACC Heart Fail 2015; 3: 59-67. https://doi.org/10.1016/j.jchf.2014.08.002

IBARROLA J, MARTÍNEZ-MARTÍNEZ E, SÁDABA JR, ARRIETA V, GARCÍA-PEÑA A, ÁLVAREZ V et al. Beneficial effects of galectin-3 blockade in vascular and aortic valve alterations in an experimental pressure overload model. Int J Mol Sci 2017; 31: 1664. https://doi.org/10.3390/ijms18081664

LALA RI, DARABANTIU D, PILAT L, PUSCHITA M. Galectin-3: A Link between myocardial and arterial stiffening in patients with acute decompensated heart failure? Arq Bras Cardiol 2016; 25: 121-129. https://doi.org/10.5935/abc.20150149

Publicado

2019-08-23

Cómo citar

Arrieta, V., Sádaba, J., Álvarez, V., Rodríguez, J., & López-Andrés, N. (2019). La galectina-3, una nueva diana terapéutica para las alteraciones cardiovasculares asociadas al desarrollo de la estenosis aórtica severa. Anales Del Sistema Sanitario De Navarra, 42(2), 199–208. https://doi.org/10.23938/ASSN.0643

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