PDF herunterladen
Int J Angiol 2019; 28(02): 071-079
DOI: 10.1055/s-0039-1687818
Invited Article: Pulmonary Arterial Hypertension
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

AGE–RAGE Stress in the Pathophysiology of Pulmonary Hypertension and its Treatment

Kailash Prasad
1   Department of Physiology, College of Medicine, University of Saskatchewan, Saskatoon, Canada
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Publikationsdatum:
19. April 2019 (online)

   Lizenzen und Reprints

Abstract

Pulmonary hypertension (PH) is a rare and fatal disease characterized by elevation of pulmonary artery pressure ≥ 25 mm Hg. There are five groups of PH: (1) pulmonary artery (PA) hypertension (PAH), (2) PH due to heart diseases, (3) PH associated with lung diseases/hypoxia, (4) PH associated with chronic obstruction of PA, and (5) PH due to unclear and/or multifactorial mechanisms. The pathophysiologic mechanisms of group 1 have been studied in detail; however, those for groups 2 to 5 are not that well known. PH pathology is characterized by smooth muscle cells (SMC) proliferation, muscularization of peripheral PA, accumulation of extracellular matrix (ECM), plexiform lesions, thromboembolism, and recanalization of thrombi. Advanced glycation end products (AGE) and its receptor (RAGE) and soluble RAGE (sRAGE) appear to be involved in the pathogenesis of PH. AGE and its interaction with RAGE induce vascular hypertrophy through proliferation of vascular SMC, accumulation of ECM, and suppression of apoptosis. Reactive oxygen species (ROS) generated by interaction of AGE and RAGE modulates SMC proliferation, attenuate apoptosis, and constricts PA. Increased stiffness in the artery due to vascular hypertrophy, and vasoconstriction due to ROS resulted in PH. The data also suggest that reduction in consumption and formation of AGE, suppression of RAGE expression, blockage of RAGE ligand binding, elevation of sRAGE levels, and antioxidants may be novel therapeutic targets for prevention, regression, and slowing of progression of PH. In conclusion, AGE–RAGE stress may be involved in the pathogenesis of PH and the therapeutic targets should be the AGE–RAGE axis.

Keywords

advanced glycation end products - cell receptor for AGE - soluble RAGE - pulmonary hypertension - pathogenesis - therapeutic targets

Disclosure

None.


 

  • References

  • 1 Simonneau G, Gatzoulis MA, Adatia I. , et al. Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol 2013; 62 (25, Suppl): D34-D41
    CrossrefPubMedGoogle Scholar
  • 2 Sysol JR, Machado RF. Classification and pathophysiology of pulmonary hypertension. Continuing Cardiol Education 2018 ;4(1)
    PubMedGoogle Scholar
  • 3 Machicao VI, Balakrishnan M, Fallon MB. Pulmonary complications in chronic liver disease. Hepatology 2014; 59 (04) 1627-1637
    CrossrefPubMedGoogle Scholar
  • 4 Wijeratne DT, Lajkosz K, Brogly SB. , et al. Increasing incidence and prevalence of world health organization groups 1 to 4 pulmonary hypertension: a population-based cohort study in Ontario, Canada. Circ Cardiovasc Qual Outcomes 2018; 11 (02) e003973
    PubMedGoogle Scholar
  • 5 Prasad K, Mishra M. Do advanced glycation end products and its receptors play a role in the pathophysiology of hypertension?. Int J Angiol 2017; 26 (01) 1-11
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 6 Prasad K. Pathophysiology and medical treatment of carotid artery stenosis. Int J Angiol 2015; 24 (03) 158-172
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 7 Prasad K, Tiwari S. Therapeutic interventions for advanced glycation end products and its receptor-mediated cardiovascular disease. Curr Pharm Des 2017; 23 (06) 937-943
    CrossrefPubMedGoogle Scholar
  • 8 McGoon MD, Benza RL, Escribano-Subias P. , et al. Pulmonary arterial hypertension: epidemiology and registries. J Am Coll Cardiol 2013; 62 (25, Suppl): D51-D59
    CrossrefPubMedGoogle Scholar
  • 9 Peacock AJ, Murphy NF, McMurray JJV, Caballero L, Stewart S. An epidemiological study of pulmonary arterial hypertension. Eur Respir J 2007; 30 (01) 104-109
    CrossrefPubMedGoogle Scholar
  • 10 Hoeper MM, Huscher D, Pittrow D. Incidence and prevalence of pulmonary arterial hypertension in Germany. Int J Cardiol 2016; 203: 612-613
    CrossrefPubMedGoogle Scholar
  • 11 Ghio S, Gavazzi A, Campana C. , et al. Independent and additive prognostic value of right ventricular systolic function and pulmonary artery pressure in patients with chronic heart failure. J Am Coll Cardiol 2001; 37 (01) 183-188
    CrossrefPubMedGoogle Scholar
  • 12 Thabut G, Dauriat G, Stern JB. , et al. Pulmonary hemodynamics in advanced COPD candidates for lung volume reduction surgery or lung transplantation. Chest 2005; 127 (05) 1531-1536
    CrossrefPubMedGoogle Scholar
  • 13 Chaouat A, Bugnet AS, Kadaoui N. , et al. Severe pulmonary hypertension and chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2005; 172 (02) 189-194
    CrossrefPubMedGoogle Scholar
  • 14 Lettieri CJ, Nathan SD, Barnett SD, Ahmad S, Shorr AF. Prevalence and outcomes of pulmonary arterial hypertension in advanced idiopathic pulmonary fibrosis. Chest 2006; 129 (03) 746-752
    CrossrefPubMedGoogle Scholar
  • 15 Escribano-Subias P, Blanco I, López-Meseguer M. , et al; REHAP investigators. Survival in pulmonary hypertension in Spain: insights from the Spanish registry. Eur Respir J 2012; 40 (03) 596-603
    CrossrefPubMedGoogle Scholar
  • 16 Pengo V, Lensing AW, Prins MH. , et al; Thromboembolic Pulmonary Hypertension Study Group. Incidence of chronic thromboembolic pulmonary hypertension after pulmonary embolism. N Engl J Med 2004; 350 (22) 2257-2264
    CrossrefPubMedGoogle Scholar
  • 17 Shorr AF, Helman DL, Davies DB, Nathan SD. Pulmonary hypertension in advanced sarcoidosis: epidemiology and clinical characteristics. Eur Respir J 2005; 25 (05) 783-788
    CrossrefPubMedGoogle Scholar
  • 18 Rich JD, Rich S. Clinical diagnosis of pulmonary hypertension. Circulation 2014; 130 (20) 1820-1830
    CrossrefPubMedGoogle Scholar
  • 19 Galiè N, Hoeper MM, Humbert M. , et al; ESC Committee for Practice Guidelines (CPG). Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J 2009; 30 (20) 2493-2537
    CrossrefPubMedGoogle Scholar
  • 20 Farber HW, Loscalzo J. Pulmonary arterial hypertension. N Engl J Med 2004; 351 (16) 1655-1665
    CrossrefPubMedGoogle Scholar
  • 21 Yuan XJ, Tod ML, Rubin LJ, Blaustein MP. Contrasting effects of hypoxia on tension in rat pulmonary and mesenteric arteries. Am J Physiol 1990; 259 (2, Pt. 2): H281-H289
    PubMedGoogle Scholar
  • 22 Humbert M, Morrell NW, Archer SL. , et al. Cellular and molecular pathobiology of pulmonary arterial hypertension. J Am Coll Cardiol 2004; 43 (12, Suppl. S): 13s-24s
    CrossrefPubMedGoogle Scholar
  • 23 Yuan JX, Rubin LJ. Pathogenesis of pulmonary arterial hypertension: the need for multiple hits. Circulation 2005; 111: 534-538
    CrossrefPubMedGoogle Scholar
  • 24 Herve P, Humbert M, Sitbon O. , et al. Pathobiology of pulmonary hypertension. The role of platelets and thrombosis. Clin Chest Med 2001; 22 (03) 451-458
    CrossrefPubMedGoogle Scholar
  • 25 Aytekin M, Aulak KS, Haserodt S. , et al. Abnormal platelet aggregation in idiopathic pulmonary arterial hypertension: role of nitric oxide. Am J Physiol Lung Cell Mol Physiol 2012; 302 (06) L512-L520
    CrossrefPubMedGoogle Scholar
  • 26 Prasad K. Soluble receptor for advanced glycation end products (sRAGE) and cardiovascular disease. Int J Angiol 2006; 15: 57-68
    PubMedGoogle Scholar
  • 27 Bucala R, Cerami A. Advanced glycosylation: chemistry, biology, and implications for diabetes and aging. Adv Pharmacol 1992; 23: 1-34
    CrossrefPubMedGoogle Scholar
  • 28 Wautier MP, Chappey O, Corda S, Stern DM, Schmidt AM, Wautier JL. Activation of NADPH oxidase by AGE links oxidant stress to altered gene expression via RAGE. Am J Physiol Endocrinol Metab 2001; 280 (05) E685-E694
    CrossrefPubMedGoogle Scholar
  • 29 Gloire G, Legrand-Poels S, Piette J. NF-kappaB activation by reactive oxygen species: fifteen years later. Biochem Pharmacol 2006; 72 (11) 1493-1505
    CrossrefPubMedGoogle Scholar
  • 30 Reznikov LL, Waksman J, Azam T. , et al. Effect of advanced glycation end products on endotoxin-induced TNF-alpha, IL-1beta and IL-8 in human peripheral blood mononuclear cells. Clin Nephrol 2004; 61 (05) 324-336
    CrossrefPubMedGoogle Scholar
  • 31 Schmidt AM, Yan SD, Brett J, Mora R, Nowygrod R, Stern D. Regulation of human mononuclear phagocyte migration by cell surface-binding proteins for advanced glycation end products. J Clin Invest 1993; 91 (05) 2155-2168
    CrossrefPubMedGoogle Scholar
  • 32 Tam XHL, Shiu SWM, Leng L, Bucala R, Betteridge DJ, Tan KCB. Enhanced expression of receptor for advanced glycation end-products is associated with low circulating soluble isoforms of the receptor in Type 2 diabetes. Clin Sci (Lond) 2011; 120 (02) 81-89
    CrossrefPubMedGoogle Scholar
  • 33 Yonekura H, Yamamoto Y, Sakurai S. , et al. Novel splice variants of the receptor for advanced glycation end-products expressed in human vascular endothelial cells and pericytes, and their putative roles in diabetes-induced vascular injury. Biochem J 2003; 370 (Pt. 3): 1097-1109
    CrossrefPubMedGoogle Scholar
  • 34 Geroldi D, Falcone C, Emanuele E. Soluble receptor for advanced glycation end products: from disease marker to potential therapeutic target. Curr Med Chem 2006; 13 (17) 1971-1978
    CrossrefPubMedGoogle Scholar
  • 35 Prasad K, Mishra M. AGE-RAGE stress, stressors, and antistressors in health and disease. Int J Angiol 2018; 27 (01) 1-12
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 36 Gopal P, Reynaert NL, Scheijen JLJM. , et al. Plasma advanced glycation end-products and skin autofluorescence are increased in COPD. Eur Respir J 2014; 43 (02) 430-438
    CrossrefPubMedGoogle Scholar
  • 37 Wu L, Ma L, Nicholson LFB, Black PN. Advanced glycation end products and its receptor (RAGE) are increased in patients with COPD. Respir Med 2011; 105 (03) 329-336
    CrossrefPubMedGoogle Scholar
  • 38 Hoonhorst SJM, Lo Tam Loi AT, Hartman JE. , et al. Advanced glycation end products in the skin are enhanced in COPD. Metabolism 2014; 63 (09) 1149-1156
    CrossrefPubMedGoogle Scholar
  • 39 Berg TJ, Snorgaard O, Faber J. , et al. Serum levels of advanced glycation end products are associated with left ventricular diastolic function in patients with type 1 diabetes. Diabetes Care 1999; 22 (07) 1186-1190
    CrossrefPubMedGoogle Scholar
  • 40 Linssen PBC, Henry RM, Schalkwijk CG. , et al. Serum advanced glycation endproducts are associated with left ventricular dysfunction in normal glucose metabolism but not in type 2 diabetes: The Hoorn Study. Diab Vasc Dis Res 2016; 13 (04) 278-285
    CrossrefPubMedGoogle Scholar
  • 41 Hegab Z, Gibbons S, Neyses L, Mamas MA. Role of advanced glycation end products in cardiovascular disease. World J Cardiol 2012; 4 (04) 90-102
    CrossrefPubMedGoogle Scholar
  • 42 Koyama Y, Takeishi Y, Arimoto T. , et al. High serum level of pentosidine, an advanced glycation end product (AGE), is a risk factor of patients with heart failure. J Card Fail 2007; 13 (03) 199-206
    CrossrefPubMedGoogle Scholar
  • 43 Moser B, Megerle A, Bekos C. , et al. Local and systemic RAGE axis changes in pulmonary hypertension: CTEPH and iPAH. PLoS One 2014; 9 (09) e106440
    CrossrefPubMedGoogle Scholar
  • 44 Jia D, He Y, Zhu Q. , et al. RAGE-mediated extracellular matrix proteins accumulation exacerbates HySu-induced pulmonary hypertension. Cardiovasc Res 2017; 113 (06) 586-597
    CrossrefPubMedGoogle Scholar
  • 45 Abdul-Salam VB, Wharton J, Cupitt J, Berryman M, Edwards RJ, Wilkins MR. Proteomic analysis of lung tissues from patients with pulmonary arterial hypertension. Circulation 2010; 122 (20) 2058-2067
    CrossrefPubMedGoogle Scholar
  • 46 Meloche J, Courchesne A, Barrier M. , et al. Critical role for the advanced glycation end-products receptor in pulmonary arterial hypertension etiology. J Am Heart Assoc 2013; 2 (01) e005157
    PubMedGoogle Scholar
  • 47 Manichaikul A, Sun L, Borczuk AC. , et al. Plasma Soluble Receptor for Advanced Glycation End Products in Idiopathic Pulmonary Fibrosis. Ann Am Thorac Soc 2017; 14 (05) 628-635
    CrossrefPubMedGoogle Scholar
  • 48 Yonchuk JG, Silverman EK, Bowler RP. , et al. Circulating soluble receptor for advanced glycation end products (sRAGE) as a biomarker of emphysema and the RAGE axis in the lung. Am J Respir Crit Care Med 2015; 192 (07) 785-792
    CrossrefPubMedGoogle Scholar
  • 49 Suzuki S, Nakazato K, Sugimoto K. , et al. Receptor for Aavanced glycation end-products and high-mobility group box 1 in patients with pulmonary hypertension. Int Heart J 2016; 57 (02) 234-240
    CrossrefPubMedGoogle Scholar
  • 50 Schmidt AM, Hasu M, Popov D. , et al. Receptor for advanced glycation end products (AGEs) has a central role in vessel wall interactions and gene activation in response to circulating AGE proteins. Proc Natl Acad Sci U S A 1994; 91 (19) 8807-8811
    CrossrefPubMedGoogle Scholar
  • 51 Tanaka S, Avigad G, Brodsky B, Eikenberry EF. Glycation induces expansion of the molecular packing of collagen. J Mol Biol 1988; 203 (02) 495-505
    CrossrefPubMedGoogle Scholar
  • 52 Striker LJ, Striker GE. Administration of AGEs in vivo induces extracellular matrix gene expression. Nephrol Dial Transplant 1996; 11 (Suppl. 05) 62-65
    PubMedGoogle Scholar
  • 53 Hogan M, Cerami A, Bucala R. Advanced glycosylation endproducts block the antiproliferative effect of nitric oxide. Role in the vascular and renal complications of diabetes mellitus. J Clin Invest 1992; 90 (03) 1110-1115
    CrossrefPubMedGoogle Scholar
  • 54 Rojas A, Romay S, González D, Herrera B, Delgado R, Otero K. Regulation of endothelial nitric oxide synthase expression by albumin-derived advanced glycosylation end products. Circ Res 2000; 86 (03) E50-E54
    PubMedGoogle Scholar
  • 55 Xu B, Chibber R, Ruggiero D, Kohner E, Ritter J, Ferro A. Impairment of vascular endothelial nitric oxide synthase activity by advanced glycation end products. FASEB J 2003; 17 (10) 1289-1291
    CrossrefPubMedGoogle Scholar
  • 56 Goldin A, Beckman JA, Schmidt AM, Creager MA. Advanced glycation end products: sparking the development of diabetic vascular injury. Circulation 2006; 114 (06) 597-605
    CrossrefPubMedGoogle Scholar
  • 57 Yamagishi S, Fujimori H, Yonekura H, Yamamoto Y, Yamamoto H. Advanced glycation endproducts inhibit prostacyclin production and induce plasminogen activator inhibitor-1 in human microvascular endothelial cells. Diabetologia 1998; 41 (12) 1435-1441
    CrossrefPubMedGoogle Scholar
  • 58 Quehenberger P, Bierhaus A, Fasching P. , et al. Endothelin 1 transcription is controlled by nuclear factor-kappaB in AGE-stimulated cultured endothelial cells. Diabetes 2000; 49 (09) 1561-1570
    CrossrefPubMedGoogle Scholar
  • 59 Ma M, Guo X, Chang Y. , et al. Advanced glycation end products promote proliferation and suppress autophagy via reduction of Cathepsin D in rat vascular smooth muscle cells. Mol Cell Biochem 2015; 403 (1,2): 73-83
    CrossrefPubMedGoogle Scholar
  • 60 Li C, Chang Y, Li Y. , et al. Advanced glycation end products promote the proliferation and migration of primary rat vascular smooth muscle cells via the upregulation of BAG3. Int J Mol Med 2017; 39 (05) 1242-1254
    CrossrefPubMedGoogle Scholar
  • 61 Yuan X, Zhang Z, Gong K, Zhao P, Qin J, Liu N. Inhibition of reactive oxygen species/extracellular signal-regulated kinases pathway by pioglitazone attenuates advanced glycation end products-induced proliferation of vascular smooth muscle cells in rats. Biol Pharm Bull 2011; 34 (05) 618-623
    CrossrefPubMedGoogle Scholar
  • 62 Greenway S, van Suylen RJ, Du Marchie Sarvaas G. , et al. S100A4/Mts1 produces murine pulmonary artery changes resembling plexogenic arteriopathy and is increased in human plexogenic arteriopathy. Am J Pathol 2004; 164 (01) 253-262
    CrossrefPubMedGoogle Scholar
  • 63 Ciuclan L, Bonneau O, Hussey M. , et al. A novel murine model of severe pulmonary arterial hypertension. Am J Respir Crit Care Med 2011; 184 (10) 1171-1182
    CrossrefPubMedGoogle Scholar
  • 64 Ranzato E, Patrone M, Pedrazzi M, Burlando B. Hmgb1 promotes wound healing of 3T3 mouse fibroblasts via RAGE-dependent ERK1/2 activation. Cell Biochem Biophys 2010; 57 (01) 9-17
    CrossrefPubMedGoogle Scholar
  • 65 Rafikova O, McBride ML, Langlais PR, Rafikov R. Receptor for advanced glycation end products (RAGE) regulates metabolic reprogramming induced over-proliferation in pulmonary hypertension. Am J Respir Crit Care Med 2018; 197: A4613
    PubMedGoogle Scholar
  • 66 Nakamura K, Sakaguchi M, Matsubara H. , et al. Crucial role of RAGE in inappropriate increase of smooth muscle cells from patients with pulmonary arterial hypertension. PLoS One 2018; 13 (09) e0203046
    CrossrefPubMedGoogle Scholar
  • 67 Bharadwaj LA, Prasad K. Mechanism of superoxide anion-induced modulation of vascular tone. Int J Angiol 2002; 11: 23-29
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 68 Bharadwaj L, Prasad K. Mediation of H2O2-induced vascular relaxation by endothelium-derived relaxing factor. Mol Cell Biochem 1995; 149-150: 267-270
    CrossrefPubMedGoogle Scholar
  • 69 Prasad K, Kalra J, Chaudhary AK, Debnath D. Effect of polymorphonuclear leukocyte-derived oxygen free radicals and hypochlorous acid on cardiac function and some biochemical parameters. Am Heart J 1990; 119 (3, Pt. 1): 538-550
    CrossrefPubMedGoogle Scholar
  • 70 Prasad K, Kalra J, Chan WP, Chaudhary AK. Effect of oxygen free radicals on cardiovascular function at organ and cellular levels. Am Heart J 1989; 117 (06) 1196-1202
    CrossrefPubMedGoogle Scholar
  • 71 Owen CA. Proteinases and oxidants as targets in the treatment of chronic obstructive pulmonary disease. Proc Am Thorac Soc 2005; 2 (04) 373-385 , discussion 394–395
    CrossrefPubMedGoogle Scholar
  • 72 Aggarwal S, Gross CM, Sharma S, Fineman JR, Black SM. Reactive oxygen species in pulmonary vascular remodeling. Compr Physiol 2013; 3 (03) 1011-1034
    CrossrefPubMedGoogle Scholar
  • 73 Jernigan NL, Naik JS, Weise-Cross L. , et al. Contribution of reactive oxygen species to the pathogenesis of pulmonary arterial hypertension. PLoS One 2017; 12 (06) e0180455
    CrossrefPubMedGoogle Scholar
  • 74 Weisenberger J. Foods high in AGEs. Available at: http://www.diabetesforecast.org/2014/11-nov/foods-high-in-ages.html . Accessed 2014
    PubMedGoogle Scholar
  • 75 Uribarri J, Woodruff S, Goodman S. , et al. Advanced glycation end products in foods and a practical guide to their reduction in the diet. J Am Diet Assoc 2010; 110 (06) 911-16.e12
    CrossrefPubMedGoogle Scholar
  • 76 Uribarri J, Cai W, Sandu O, Peppa M, Goldberg T, Vlassara H. Diet-derived advanced glycation end products are major contributors to the body's AGE pool and induce inflammation in healthy subjects. Ann N Y Acad Sci 2005; 1043: 461-466
    CrossrefPubMedGoogle Scholar
  • 77 Prasad K, Dhar I, Caspar-Bell G, Prasad K, Dhar I, Caspar-Bell G. Role of advanced glycation end products and its receptors in the pathogenesis of cigarette smoke-induced cardiovascular disease. Int J Angiol 2015; 24 (02) 75-80
    PubMedGoogle Scholar
  • 78 Hammes HP, Du X, Edelstein D. , et al. Benfotiamine blocks three major pathways of hyperglycemic damage and prevents experimental diabetic retinopathy. Nat Med 2003; 9 (03) 294-299
    CrossrefPubMedGoogle Scholar
  • 79 Metz TO, Alderson NL, Thorpe SR, Baynes JW. Pyridoxamine, an inhibitor of advanced glycation and lipoxidation reactions: a novel therapy for treatment of diabetic complications. Arch Biochem Biophys 2003; 419 (01) 41-49
    CrossrefPubMedGoogle Scholar
  • 80 Subratty AH, Aukburally N, Jowaheer V, Joonus N. Vitamin C and urea inhibit the formation of advanced glycation end products in vitro. Nutr Food Sci 2010; 40: 456-465
    CrossrefPubMedGoogle Scholar
  • 81 Salum E, Kals J, Kampus P. , et al. Vitamin D reduces deposition of advanced glycation end-products in the aortic wall and systemic oxidative stress in diabetic rats. Diabetes Res Clin Pract 2013; 100 (02) 243-249
    CrossrefPubMedGoogle Scholar
  • 82 Baragetti I, Furiani S, Vettoretti S. , et al. Role of vitamin E-coated membrane in reducing advanced glycation end products in hemodialysis patients: a pilot study. Blood Purif 2006; 24 (04) 369-376
    CrossrefPubMedGoogle Scholar
  • 83 Klebanov GI, Teselkin YuO, Babenkova IV. , et al. Effect of carnosine and its components on free-radical reactions. Membr Cell Biol 1998; 12 (01) 89-99
    PubMedGoogle Scholar
  • 84 Price DL, Rhett PM, Thorpe SR, Baynes JW. Chelating activity of advanced glycation end-product inhibitors. J Biol Chem 2001; 276 (52) 48967-48972
    CrossrefPubMedGoogle Scholar
  • 85 Hipkiss AR. Carnosine and protein carbonyl groups: a possible relationship. Biochemistry (Mosc) 2000; 65 (07) 771-778
    PubMedGoogle Scholar
  • 86 Ramful D, Tarnus E, Rondeau P, Da Silva CR, Bahorun T, Bourdon E. Citrus fruit extracts reduce advanced glycation end products (AGEs)- and H2O2-induced oxidative stress in human adipocytes. J Agric Food Chem 2010; 58 (20) 11119-11129
    CrossrefPubMedGoogle Scholar
  • 87 Liu W, Ma H, Frost L, Yuan T, Dain JA, Seeram NP. Pomegranate phenolics inhibit formation of advanced glycation endproducts by scavenging reactive carbonyl species. Food Funct 2014; 5 (11) 2996-3004
    CrossrefPubMedGoogle Scholar
  • 88 Mannervik B. Molecular enzymology of the glyoxalase system. Drug Metabol Drug Interact 2008; 23 (1,2): 13-27
    CrossrefPubMedGoogle Scholar
  • 89 Shinohara M, Thornalley PJ, Giardino I. , et al. Overexpression of glyoxalase-I in bovine endothelial cells inhibits intracellular advanced glycation endproduct formation and prevents hyperglycemia-induced increases in macromolecular endocytosis. J Clin Invest 1998; 101 (05) 1142-1147
    CrossrefPubMedGoogle Scholar
  • 90 Cai W, He JC, Zhu L, Lu C, Vlassara H. Advanced glycation end product (AGE) receptor 1 suppresses cell oxidant stress and activation signaling via EGF receptor. Proc Natl Acad Sci U S A 2006; 103 (37) 13801-13806
    CrossrefPubMedGoogle Scholar
  • 91 Cuccurullo C, Iezzi A, Fazia ML. , et al. Suppression of RAGE as a basis of simvastatin-dependent plaque stabilization in type 2 diabetes. Arterioscler Thromb Vasc Biol 2006; 26 (12) 2716-2723
    CrossrefPubMedGoogle Scholar
  • 92 Xu L, Zang P, Feng B, Qian Q. Atorvastatin inhibits the expression of RAGE induced by advanced glycation end products on aortas in healthy Sprague-Dawley rats. Diabetol Metab Syndr 2014; 6 (01) 102
    CrossrefPubMedGoogle Scholar
  • 93 Nakamura K, Yamagishi S, Nakamura Y. , et al. Telmisartan inhibits expression of a receptor for advanced glycation end products (RAGE) in angiotensin-II-exposed endothelial cells and decreases serum levels of soluble RAGE in patients with essential hypertension. Microvasc Res 2005; 70 (03) 137-141
    CrossrefPubMedGoogle Scholar
  • 94 Fan Q, Liao J, Kobayashi M. , et al. Candesartan reduced advanced glycation end-products accumulation and diminished nitro-oxidative stress in type 2 diabetic KK/Ta mice. Nephrol Dial Transplant 2004; 19 (12) 3012-3020
    CrossrefPubMedGoogle Scholar
  • 95 Marx N, Walcher D, Ivanova N. , et al. Thiazolidinediones reduce endothelial expression of receptors for advanced glycation end products. Diabetes 2004; 53 (10) 2662-2668
    CrossrefPubMedGoogle Scholar
  • 96 Yamagishi S, Takeuchi M. Nifedipine inhibits gene expression of receptor for advanced glycation end products (RAGE) in endothelial cells by suppressing reactive oxygen species generation. Drugs Exp Clin Res 2004; 30 (04) 169-175
    PubMedGoogle Scholar
  • 97 Lin J, Tang Y, Kang Q, Feng Y, Chen A. Curcumin inhibits gene expression of receptor for advanced glycation end-products (RAGE) in hepatic stellate cells in vitro by elevating PPARγ activity and attenuating oxidative stress. Br J Pharmacol 2012; 166 (08) 2212-2227
    CrossrefPubMedGoogle Scholar
  • 98 TransTech Pharma LLC. Available at: https://bciq.biocentury.com/companies/transtech_pharma_llc . Accessed on March 25, 2019
    PubMed
  • 99 Bongarzone S, Savickas V, Luzi F, Gee AD. Targeting the Receptor for Advanced Glycation Endproducts (RAGE): A Medicinal Chemistry Perspective. J Med Chem 2017; 60 (17) 7213-7232
    CrossrefPubMedGoogle Scholar
  • 100 Zong H, Madden A, Ward M, Mooney MH, Elliott CT, Stitt AW. Homodimerization is essential for the receptor for advanced glycation end products (RAGE)-mediated signal transduction. J Biol Chem 2010; 285 (30) 23137-23146
    CrossrefPubMedGoogle Scholar
  • 101 Nozue T, Yamagishi S-I, Takeuchi M. , et al. Effect of statins on the serum soluble form of receptor for advanced glycation end- products and its association with coronary atherosclerosis in patients with angina pectoris. IJC Metab Endocr 2014; 4: 47-52
    CrossrefPubMedGoogle Scholar
  • 102 Quade-Lyssy P, Kanarek AM, Baiersdörfer M, Postina R, Kojro E. Statins stimulate the production of a soluble form of the receptor for advanced glycation end products. J Lipid Res 2013; 54 (11) 3052-3061
    CrossrefPubMedGoogle Scholar
  • 103 Forbes JM, Thorpe SR, Thallas-Bonke V. , et al. Modulation of soluble receptor for advanced glycation end products by angiotensin-converting enzyme-1 inhibition in diabetic nephropathy. J Am Soc Nephrol 2005; 16 (08) 2363-2372
    CrossrefPubMedGoogle Scholar
  • 104 Tan KCB, Chow WS, Tso AWK. , et al. Thiazolidinedione increases serum soluble receptor for advanced glycation end-products in type 2 diabetes. Diabetologia 2007; 50 (09) 1819-1825
    CrossrefPubMedGoogle Scholar
  • 105 Irani M, Minkoff H, Seifer DB, Merhi Z. Vitamin D increases serum levels of the soluble receptor for advanced glycation end products in women with PCOS. J Clin Endocrinol Metab 2014; 99 (05) E886-E890
    CrossrefPubMedGoogle Scholar
  • 106 Park L, Raman KG, Lee KJ. , et al. Suppression of accelerated diabetic atherosclerosis by the soluble receptor for advanced glycation endproducts. Nat Med 1998; 4 (09) 1025-1031
    CrossrefPubMedGoogle Scholar
  • 107 Sakaguchi T, Yan SF, Yan SD. , et al. Central role of RAGE-dependent neointimal expansion in arterial restenosis. J Clin Invest 2003; 111 (07) 959-972
    CrossrefPubMedGoogle Scholar
  • 108 Wautier JL, Zoukourian C, Chappey O. , et al. Receptor-mediated endothelial cell dysfunction in diabetic vasculopathy. Soluble receptor for advanced glycation end products blocks hyperpermeability in diabetic rats. J Clin Invest 1996; 97 (01) 238-243
    CrossrefPubMedGoogle Scholar
  • 109 Santilli F, Vazzana N, Bucciarelli LG, Davì G. Soluble forms of RAGE in human diseases: clinical and therapeutical implications. Curr Med Chem 2009; 16 (08) 940-952
    CrossrefPubMedGoogle Scholar
  • 110 Vonk-Noordegraaf A, Haddad F, Chin KM. , et al. Right heart adaptation to pulmonary arterial hypertension: physiology and pathobiology. J Am Coll Cardiol 2013; 62 (25, Suppl.): D22-D33
    CrossrefPubMedGoogle Scholar
  • 111 Ryan JJ, Archer SL. The right ventricle in pulmonary arterial hypertension: disorders of metabolism, angiogenesis and adrenergic signaling in right ventricular failure. Circ Res 2014; 115 (01) 176-188
    CrossrefPubMedGoogle Scholar
  • 112 de Matos Cavalcante AG, de Bruin PF, de Bruin VM. , et al. Melatonin reduces lung oxidative stress in patients with chronic obstructive pulmonary disease: a randomized, double-blind, placebo-controlled study. J Pineal Res 2012; 53 (03) 238-244
    CrossrefPubMedGoogle Scholar
  • 113 Jin H, Wang Y, Zhou L. , et al. Melatonin attenuates hypoxic pulmonary hypertension by inhibiting the inflammation and the proliferation of pulmonary arterial smooth muscle cells. J Pineal Res 2014; 57 (04) 442-450
    CrossrefPubMedGoogle Scholar
  • 114 Maarman G, Blackhurst D, Thienemann F. , et al. Melatonin as a preventive and curative therapy against pulmonary hypertension. J Pineal Res 2015; 59 (03) 343-353
    CrossrefPubMedGoogle Scholar
  • 115 Maarman GJ. Natural antioxidants as potential therapy, and a promising role for melatonin against pulmonary hypertension. Adv Exp Med Biol 2017; 967: 161-178 . doi:10.1007/978-3-319-63245-2-10
    PubMedGoogle Scholar
  • 116 Prasad K. Low levels of serum soluble receptors for advanced glycation end products, biomarkers for disease state: myth or reality. Int J Angiol 2014; 23 (01) 11-16
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 117 Prasad K. Is there any evidence that AGE/sRAGE is a universal biomarker/risk marker for diseases?. Mol Cell Biochem 2019; 451 (1,2): 139-144
    CrossrefPubMedGoogle Scholar