Dipeptidyl peptidase-4 inhibition with linagliptin prevents western diet-induced vascular abnormalities in female mice

Cardiovascular Diabetology

Volumn 15, Issue 1, 2016, Pages

  Manrique, Camila ^a,b   Habibi, Javad ^a,b   Aroor, Annayya R ^a,b   Sowers, James R ^a,b,c   Jia, Guanghong ^a,b   Hayden, Melvin R ^a   Garro, Mona ^a,b   Martinez Lemus, Luis A ^a,c   Ramirez Perez, Francisco I ^a,c   Klein, Thomas ^d   Meininger, Gerald A ^a,c   DeMarco, Vincent G ^a,b,c  

^a University of Missouri   (United States)

^b VETERANS AFFAIRS MEDICAL CENTER   (United States)

^c UNIVERSITY OF MISSOURI   (United States)

^d BOEHRINGER INGELHEIM PHARMA GMBH AND CO KG   (Germany)

Author keywords

Atomic force microscopy; Pulse wave velocity

Indexed keywords

DIPEPTIDYL PEPTIDASE IV; FIBROBLAST GROWTH FACTOR 23; KLOTHO PROTEIN; LINAGLIPTIN; ANTIDIABETIC AGENT; DIPEPTIDYL PEPTIDASE IV INHIBITOR;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; AORTA DISEASE; ARTERIAL STIFFNESS; ARTERIAL WALL THICKENING; ARTICLE; ATOMIC FORCE MICROSCOPY; C57BL 6 MOUSE; CELL ULTRASTRUCTURE; CONTROLLED STUDY; DOPPLER FLOWMETRY; ENDOTHELIAL DYSFUNCTION; ENDOTHELIUM CELL; ENZYME INHIBITION; EX VIVO STUDY; FEMALE; FIBROSIS; IMMUNOHISTOCHEMISTRY; MOUSE; NONHUMAN; OXIDATIVE STRESS; PULSE WAVE; TREATMENT RESPONSE; VASCULAR ENDOTHELIUM; VASODILATATION; VASOMOTOR REFLEX; WESTERN DIET; ANIMAL; AORTA; C57BL MOUSE; COMPLICATION; DRUG EFFECTS; METABOLISM; OBESITY; PHYSIOLOGY; VASCULAR REMODELING;

ANIMALS; AORTA; DIET, WESTERN; DIPEPTIDYL-PEPTIDASE IV INHIBITORS; ENDOTHELIAL CELLS; FEMALE; HYPOGLYCEMIC AGENTS; LINAGLIPTIN; MICE, INBRED C57BL; OBESITY; PULSE WAVE ANALYSIS; VASCULAR REMODELING; VASCULAR STIFFNESS; VASODILATION;

EID: 84991810131     PISSN: None     EISSN: 14752840     Source Type: Journal    
DOI: 10.1186/s12933-016-0414-5     Document Type: Article

References (63)

1. Coutinho T. Arterial stiffness and its clinical implications in women. Can J Cardiol. 2014;30:756-64.
2. Weisbrod RM, Shiang T, Alsayah L, Fry JL, Bajpai S, Reinhartking CA, Lob HE, Santhanam L, Mitchell G, Cohen RA, Seta F. Arterial stiffening precedes systolic hypertension in diet-induced obesity. Hypertension. 2013;62:1105-10.
3. Webb DR, Khunti K, Silverman R, Gray LJ, Srinivasan B, Lacy PS, Williams B, Davies MJ. Impact of metabolic indices on central artery stiffness: independent association of insulin resistance and glucose with aortic pulse wave velocity. Diabetologia. 2010;53:1190-8.
4. Park JS, Nam JS, Cho MH, Yoo JS, Ahn CW, Jee SH, Lee HS, Cha BS, Kim KR, Lee HC. Insulin resistance independently influences arterial stiffness in normoglycemic normotensive postmenopausal women. Menopause (NY). 2010;17:779-84.
5. Malik VS, Popkin BM, Bray GA, Despres JP, Willett WC, Hu FB. Sugar-sweetened beverages and risk of metabolic syndrome and type 2 diabetes: a meta-analysis. Diabetes Care. 2010;33:2477-83.
6. Malik VS, Hu FB. Fructose and cardiometabolic health: what the evidence from sugar-sweetened beverages tells us. J Am Coll Cardiol. 2015;66:1615-24.
7. Aroor AR, Demarco VG, Jia G, Sun Z, Nistala R, Meininger GA, Sowers JR. The role of tissue Renin-Angiotensin-aldosterone system in the development of endothelial dysfunction and arterial stiffness. Front Endocrinol. 2013;4:161.
8. Leopold JA. Cellular and molecular mechanisms of arterial stiffness associated with obesity. Hypertension. 2013;62:1003-4.
9. DeMarco VG, Habibi J, Jia G, Aroor AR, Ramirez-Perez FI, Martinez-Lemus LA, Bender SB, Garro M, Hayden MR, Sun Z, Meininger GA, Manrique C, Whaley-Connell A, Sowers JR. Low-dose mineralocorticoid receptor blockade prevents western diet-induced arterial stiffening in female mice. Hypertension. 2015;66:99-107.
10. Jose T, Inzucchi SE. Cardiovascular effects of the DPP-4 inhibitors. Diabetes Vasc Dis Res. 2012;9:109-16.
11. Aroor AR, Sowers JR, Jia G, DeMarco VG. Pleiotropic effects of the dipeptidylpeptidase-4 inhibitors on the cardiovascular system. Am J Physiol Heart Circ Physiol. 2014;307:H477-92.
12. Aroor AR, Sowers JR, Bender SB, Nistala R, Garro M, Mugerfeld I, Hayden MR, Johnson MS, Salam M, Whaley-Connell A, Demarco VG. Dipeptidylpeptidase inhibition is associated with improvement in blood pressure and diastolic function in insulin-resistant male Zucker obese rats. Endocrinology. 2013;154:2501-13.
13. Eckhardt M, Langkopf E, Mark M, Tadayyon M, Thomas L, Nar H, Pfrengle W, Guth B, Lotz R, Sieger P, Fuchs H, Himmelsbach F. 8-(3-(R)-aminopiperidin-1-yl)-7-but-2-ynyl-3-methyl-1-(4-methyl-quinazolin-2-ylme thyl)-3,7-dihydropurine-2,6-dione (BI 1356), a highly potent, selective, long-acting, and orally bioavailable DPP-4 inhibitor for the treatment of type 2 diabetes. J Med Chem. 2007;50:6450-3.
14. Kroller-Schon S, Knorr M, Hausding M, Oelze M, Schuff A, Schell R, Sudowe S, Scholz A, Daub S, Karbach S, Kossmann S, Gori T, Wenzel P, Schulz E, Grabbe S, Klein T, Munzel T, Daiber A. Glucose-independent improvement of vascular dysfunction in experimental sepsis by dipeptidyl-peptidase 4 inhibition. Cardiovasc Res. 2012;96:140-9.
15. Nistala R, Habibi J, Lastra G, Manrique C, Aroor AR, Hayden MR, Garro M, Meuth A, Johnson M, Whaley-Connell A, Sowers JR. Prevention of obesityinduced renal injury in male mice by DPP4 inhibition. Endocrinology. 2014;155:2266-76.
16. Zhou X, Ma L, Habibi J, Whaley-Connel AT, Hayden MR, Tilmon RD, Brown AN, DeMarco VG, Sowers JR. Nebivolol improves diastolic dysfunction and myocardial tissue remodeling through reductions in oxidative stress in the Zucker Obese rat. Hypertension. 2010;55:880-8.
17. Wei Y, Whaley-Connell AT, Habibi J, Rehmer J, Rehmer N, Patel K, Hayden M, DeMarco V, Ferrario CM, Ibdah JA, Sowers JR. Mineralocorticoid receptor antagonism attenuates vascular apoptosis and injury via rescuing protein kinase B activation. Hypertension. 2009;53:158-65.
18. Llaurado G, Ceperuelo-Mallafre V, Vilardell C, Simo R, Gil P, Cano A, Vendrell J, Gonzalez-Clemente JM. Advanced glycation end products are associated with arterial stiffness in type 1 diabetes. J Endocrinol. 2014;221:405-13.
19. Goldin A, Beckman JA, Schmidt AM, Creager MA. Advanced glycation end products: sparking the development of diabetic vascular injury. Circulation. 2006;114:597-605.
20. Huveneers S, Daemen MJ, Hordijk PL. Between Rho(k) and a hard place: the relation between vessel wall stiffness, endothelial contractility, and cardiovascular disease. Circ Res. 2015;116:895-908.
21. Kestenbaum B, Sachs MC, Hoofnagle AN, Siscovick DS, Ix JH, Robinson-Cohen C, Lima JA, Polak JF, Blondon M, Ruzinski J, Rock D, de Boer IH. Fibroblast growth factor-23 and cardiovascular disease in the general population: the multi-ethnic study of atherosclerosis. Circ Heart Fail. 2014;7:409-17.
22. di Giuseppe R, Kuhn T, Hirche F, Buijsse B, Dierkes J, Fritsche A, Kaaks R, Boeing H, Stangl GI, Weikert C. Potential predictors of plasma fibroblast growth factor 23 concentrations: cross-sectional analysis in the EPICgermany study. PLoS ONE. 2015;10:e0133580.
23. Lutsey PL, Alonso A, Selvin E, Pankow JS, Michos ED, Agarwal SK, Loehr LR, Eckfeldt JH, Coresh J. Fibroblast growth factor-23 and incident coronary heart disease, heart failure, and cardiovascular mortality: the atherosclerosis risk in communities study. J Am Heart Assoc. 2014;3:e000936.
24. Jia G, Habibi J, Aroor AR, Martinezlemus LA, DeMarco VG, Ramirez-Perez FI, Sun Z, Hayden MR, Meininger GA, Barrettmueller KV, Jaffe IZ, Sowers JR. Endothelial mineralocorticoid receptor mediates diet induced aortic stiffness in females. Circ Res. 2016;118:935.
25. Kanasaki K, Shi S, Kanasaki M, He J, Nagai T, Nakamura Y, Ishigaki Y, Kitada M, Srivastava SP, Koya D. Linagliptin-mediated DPP-4 inhibition ameliorates kidney fibrosis in streptozotocin-induced diabetic mice by inhibiting endothelial-to-mesenchymal transition in a therapeutic regimen. Diabetes. 2014;63:2120-31.
26. Sharkovska Y, Reichetzeder C, Alter M, Tsuprykov O, Bachmann S, Secher T, Klein T, Hocher B. Blood pressure and glucose independent renoprotective effects of dipeptidyl peptidase-4 inhibition in a mouse model of type-2 diabetic nephropathy. J Hypertension. 2014;32:2211-23.
27. Hamdani N, Hervent AS, Vandekerckhove L, Matheeussen V, Demolder M, Baerts L, De Meester I, Linke WA, Paulus WJ, De Keulenaer GW. Left ventricular diastolic dysfunction and myocardial stiffness in diabetic mice is attenuated by inhibition of dipeptidyl peptidase 4. Cardiovasc Res. 2014;104:423-31 (discussion 2223-2227).
28. Bostick B, Habibi J, Ma L, Aroor A, Rehmer N, Hayden MR, Sowers JR. Dipeptidyl peptidase inhibition prevents diastolic dysfunction and reduces myocardial fibrosis in a mouse model of Western diet induced obesity. Metab Clin Exp. 2014;63:1000-11.
29. Vanhoutte PM. Endothelium and control of vascular function. State of the Art lecture. Hypertension. 1989;13:658-67.
30. Chataigneau T, Feletou M, Huang PL, Fishman MC, Duhault J, Vanhoutte PM. Acetylcholine-induced relaxation in blood vessels from endothelial nitric oxide synthase knockout mice. Br J Pharmacol. 1999;126:219-26.
31. DeMarco VG, Aroor AR, Sowers JR. The pathophysiology of hypertension in patients with obesity. Nat Rev Endocrinol. 2014;10:364-76.
32. Ma M, Hasegawa Y, Koibuchi N, Toyama K, Uekawa K, Nakagawa T, Lin B, Kim-Mitsuyama S. DPP-4 inhibition with linagliptin ameliorates cognitive impairment and brain atrophy induced by transient cerebral ischemia in type 2 diabetic mice. Cardiovasc Diabetol. 2015;14:54.
33. Salim HM, Fukuda D, Higashikuni Y, Tanaka K, Hirata Y, Yagi S, Soeki T, Shimabukuro M, Sata M. Dipeptidyl peptidase-4 inhibitor, linagliptin, ameliorates endothelial dysfunction and atherogenesis in normoglycemic apolipoprotein-E deficient mice. Vasc Pharmacol. 2015;79:16.
34. Zeng Y, Li C, Guan M, Zheng Z, Li J, Xu W, Wang L, He F, Xue Y. The DPP-4 inhibitor sitagliptin attenuates the progress of atherosclerosis in apolipoprotein-E-knockout mice via AMPK-and MAPK-dependent mechanisms. Cardiovasc Diabetol. 2014;13:32.
35. Pojoga LH, Yao TM, Sinha S, Ross RL, Lin JC, Raffetto JD, Adler GK, Williams GH, Khalil RA. Effect of dietary sodium on vasoconstriction and eNOSmediated vascular relaxation in caveolin-1-deficient mice. Am J Physiol Heart Circ Physiol. 2008;294:H1258-65.
36. Pojoga LH, Adamova Z, Kumar A, Stennett AK, Romero JR, Adler GK, Williams GH, Khalil RA. Sensitivity of NOS-dependent vascular relaxation pathway to mineralocorticoid receptor blockade in caveolin-1-deficient mice. Am J Physiol Heart Circ Physiol. 2010;298:H1776-88.
37. Pojoga LH, Yao TM, Opsasnick LA, Garza AE, Reslan OM, Adler GK, Williams GH, Khalil RA. Dissociation of hyperglycemia from altered vascular contraction and relaxation mechanisms in caveolin-1 null mice. J Pharmacol Exp Ther. 2014;348:260-70.
38. Terawaki Y, Nomiyama T, Kawanami T, Hamaguchi Y, Takahashi H, Tanaka T, Murase K, Nagaishi R, Tanabe M, Yanase T. Dipeptidyl peptidase-4 inhibitor linagliptin attenuates neointima formation after vascular injury. Cardiovasc Diabetol. 2014;13:154.
39. Mirza MA, Alsio J, Hammarstedt A, Erben RG, Michaelsson K, Tivesten A, Marsell R, Orwoll E, Karlsson MK, Ljunggren O, Mellstrom D, Lind L, Ohlsson C, Larsson TE. Circulating fibroblast growth factor-23 is associated with fat mass and dyslipidemia in two independent cohorts of elderly individuals. Arterioscler Thromb Vasc Biol. 2011;31:219-27.
40. Hanks LJ, Casazza K, Judd SE, Jenny NS, Gutierrez OM. Associations of fibroblast growth factor-23 with markers of inflammation, insulin resistance and obesity in adults. PLoS ONE. 2015;10:e0122885.
41. Tsao CW, Pencina KM, Massaro JM, Benjamin EJ, Levy D, Vasan RS, Hoffmann U, O'Donnell CJ, Mitchell GF. Cross-sectional relations of arterial stiffness, pressure pulsatility, wave reflection, and arterial calcification. Arterioscler Thromb Vasc Biol. 2014;34:2495-500.
42. Fang Y, Ginsberg C, Seifert M, Agapova O, Sugatani T, Register TC, Freedman BI, Monier-Faugere MC, Malluche H, Hruska KA. CKD-induced wingless/integration1 inhibitors and phosphorus cause the CKD-mineral and bone disorder. J Am Soc Nephrol. 2014;25:1760-73.
43. Silswal N, Touchberry CD, Daniel DR, McCarthy DL, Zhang S, Andresen J, Stubbs JR, Wacker MJ. FGF23 directly impairs endothelium-dependent vasorelaxation by increasing superoxide levels and reducing nitric oxide bioavailability. Am J Physiol Endocrinol Metab. 2014;307:E426-36.
44. Urakawa I, Yamazaki Y, Shimada T, Iijima K, Hasegawa H, Okawa K, Fujita T, Fukumoto S, Yamashita T. Klotho converts canonical FGF receptor into a specific receptor for FGF23. Nature. 2006;444:770-4.
45. Lin Y, Chen J, Sun Z. Antiaging gene Klotho deficiency promoted high-fat diet-induced arterial stiffening via inactivation of AMP-activated protein kinase. Hypertension. 2016;67:564.
46. Izbeki F, Asuzu DT, Lorincz A, Bardsley MR, Popko LN, Choi KM, Young DL, Hayashi Y, Linden DR, Kuro-O M, Farrugia G, Ordog T. Loss of Kitlow progenitors, reduced stem cell factor and high oxidative stress underlie gastric dysfunction in progeric mice. J Physiol. 2010;588:3101-17.
47. Wang Y, Kuro-O M, Sun Z. Klotho gene delivery suppresses Nox2 expression and attenuates oxidative stress in rat aortic smooth muscle cells via the cAMP-PKA pathway. Aging Cell. 2012;11:410-7.
48. Salim HM, Fukuda D, Higashikuni Y, Tanaka K, Hirata Y, Yagi S, Soeki T, Shimabukuro M, Sata M. Dipeptidyl peptidase-4 inhibitor, linagliptin, ameliorates endothelial dysfunction and atherogenesis in normoglycemic apolipoprotein-E deficient mice. Vascul Pharmacol. 2016;79:16-23.
49. Hansen HH, Hansen G, Paulsen S, Vrang N, Mark M, Jelsing J, Klein T. The DPP-IV inhibitor linagliptin and GLP-1 induce synergistic effects on body weight loss and appetite suppression in the diet-induced obese rat. Eur J Pharmacol. 2014;741:254-63.
50. Barnett AH, Huisman H, Jones R, von Eynatten M, Patel S, Woerle HJ. Linagliptin for patients aged 70 years or older with type 2 diabetes inadequately controlled with common antidiabetes treatments: a randomised, double-blind, placebo-controlled trial. Lancet. 2013;382:1413-23.
51. Yki-Jarvinen H, Rosenstock J, Duran-Garcia S, Pinnetti S, Bhattacharya S, Thiemann S, Patel S, Woerle HJ. Effects of adding linagliptin to basal insulin regimen for inadequately controlled type 2 diabetes: a >/=52-week randomized, double-blind study. Diabetes Care. 2013;36:3875-81.
52. Gallwitz B, Rosenstock J, Rauch T, Bhattacharya S, Patel S, von Eynatten M, Dugi KA, Woerle HJ. 2-year efficacy and safety of linagliptin compared with glimepiride in patients with type 2 diabetes inadequately controlled on metformin: a randomised, double-blind, non-inferiority trial. Lancet. 2012;380:475-83.
53. Manrique C, Demarco VG, Aroor AR, Mugerfeld I, Garro M, Habibi J, Hayden MR, Sowers JR. Obesity and insulin resistance induce early development of diastolic dysfunction in young female mice fed a western diet. Endocrinology. 2013;154:3632-42.
54. Yan SF, Ramasamy R, Schmidt AM. The RAGE axis: a fundamental mechanism signaling danger to the vulnerable vasculature. Circ Res. 2010;106:842-53.
55. Ishibashi Y, Matsui T, Maeda S, Higashimoto Y, Yamagishi S. Advanced glycation end products evoke endothelial cell damage by stimulating soluble dipeptidyl peptidase-4 production and its interaction with mannose 6-phosphate/insulin-like growth factor II receptor. Cardiovasc Diabetol. 2013;12:125.
56. Li L, Li S, Deng K, Liu J, Vandvik PO, Zhao P, Zhang L, Shen J, Bala MM, Sohani ZN, Wong E, Busse JW, Ebrahim S, Malaga G, Rios LP, Wang Y, Chen Q, Guyatt GH, Sun X. Dipeptidyl peptidase-4 inhibitors and risk of heart failure in type 2 diabetes: systematic review and meta-analysis of randomised and observational studies. BMJ. 2016;352:i610.
57. Filion KB, Azoulay L, Platt RW, Dahl M, Dormuth CR, Clemens KK, Hu N, Paterson JM, Targownik L, Turin TC, Udell JA, Ernst P, Investigators C. A multicenter observational study of incretin-based drugs and heart failure. N Engl J Med. 2016;374:1145-54.
58. Scirica BM, Bhatt DL, Braunwald E, Steg PG, Davidson J, Hirshberg B, Ohman P, Frederich R, Wiviott SD, Hoffman EB, Cavender MA, Udell JA, Desai NR, Mosenzon O, McGuire DK, Ray KK, Leiter LA, Raz I. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. New Engl J Med. 2013;369:1317-26.
59. Scirica BM, Braunwald E, Raz I, Cavender MA, Morrow DA, Jarolim P, Udell JA, Mosenzon O, Im K, Umez-Eronini AA, Pollack PS, Hirshberg B, Frederich R, Lewis BS, McGuire DK, Davidson J, Steg PG, Bhatt DL. Heart failure, saxagliptin, and diabetes mellitus: observations from the SAVOR-TIMI 53 randomized trial. Circulation. 2014;130:1579-88.
60. White WB, Cannon CP, Heller SR, Nissen SE, Bergenstal RM, Bakris GL, Perez AT, Fleck PR, Mehta CR, Kupfer S, Wilson C, Cushman WC, Zannad F. Alogliptin after acute coronary syndrome in patients with type 2 diabetes. New Engl J Med. 2013;369:1327-35.
61. Zannad F, Cannon CP, Cushman WC, Bakris GL, Menon V, Perez AT, Fleck PR, Mehta CR, Kupfer S, Wilson C, Lam H, White WB, Investigators E. Heart failure and mortality outcomes in patients with type 2 diabetes taking alogliptin versus placebo in EXAMINE: a multicentre, randomised, double-blind trial. Lancet. 2015;385:2067-76.
62. Green JB, Bethel MA, Armstrong PW, Buse JB, Engel SS, Garg J, Josse R, Kaufman KD, Koglin J, Korn S, Lachin JM, McGuire DK, Pencina MJ, Standl E, Stein PP, Suryawanshi S, Vande Werf F, Peterson ED, Holman RR, Group TS. Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2015;373:232-42.
63. Rosenstock J, Marx N, Neubacher D, Seck T, Patel S, Woerle HJ, Johansen OE. Cardiovascular safety of linagliptin in type 2 diabetes: a comprehensive patient-level pooled analysis of prospectively adjudicated cardiovascular events. Cardiovasc Diabetol. 2015;14:57.