Peroxisome proliferator-activated receptor-γ: therapeutic target for diseases beyond diabetes: quo vadis?

Bibliography

• MANGELSDORF DJ, THUMMEL C, BEATO M et al.: The nuclear receptor superfamily: the second decade. Cell (1995) 83:835–839.
   PubMed Web of Science ®Google Scholar
• ••Overview of the molecular biology ofnuclear transcription factors and orphan receptors, best for newcomers to the area.
   Google Scholar
• WILLSON TM, BROWN PJ, STERNBACH DD, HENKE BR: The PPARs: from orphan receptors to drug discovery. j Med. Chem. (2000) 43:527–550.
   PubMed Web of Science ®Google Scholar
• ••Excellent overview of PPARs, PPARligands and the structural biology of PPAR receptors.
   Google Scholar
• WILLSON TM, LAMBERT MH, KLIEWER SA: PPARy and metabolic disease. Ann. Rev Biochem. (2001) 70:341–367.
   PubMed Web of Science ®Google Scholar
• BERGER J, MOLLER DE: The mechanisms of action of PPARs. Ann. Rev Med. (2002) 53:409–435.
   PubMed Web of Science ®Google Scholar
• •Good overview of the molecular mechanisms of PPAR action and their role in the pathophysiology of chronic disease.
   Google Scholar
• PERSHADSINGH HA: PPARy ligands: emerging clinical indications beyond diabetes. Expert Opin. Investig. Drugs (1999) 8:1859–1872.
   PubMedGoogle Scholar
• MILLER AR, ETGEN GJ: Novel PPAR ligands for Type 2 diabetes and the metabolic syndrome. Expert Opin. Investig. Drugs (2003) 12:1489–1500.
   PubMed Web of Science ®Google Scholar
• ••Excellent overview of PPAR ligands in preclinical and clinical development.
   Google Scholar
• HACKAM DG, ANAND SS. Emerging risk factors for atherosclerotic vascular disease: a critical review of the evidence. JAMA (2003) 290:932–940.
   PubMed Web of Science ®Google Scholar
• PLUTZKY J: The potential role of PPARs on inflammation in Type 2 diabetes mellitus and atherosclerosis. Am. J. Cardiol (2003) 92:34J–41J.
   Google Scholar
• DAYNES RA, JONES DC. Emerging roles of PPARs in inflammation and immunity. Nat. Rev Immunol (2002) 2:748–759.
   PubMed Web of Science ®Google Scholar
• ••Excellent review of PPARs, PPAR ligandsand the integration with anti-inflammatory and immunomodulatory signalling pathways.
   Google Scholar
• MORIKANG E, BENSON SC, KURTZ TW, PERSHADSINGH HA: Effects of thiazolidinediones on growth and differentiation of human aorta and coronary myocytes. Am. J. Hypertens. (1997) 10(4)440–446.
   Google Scholar
• GLASS CK, WITZTUM JL. Atherosclerosis, the road ahead. Cell. (2001) 104:503–516.
   PubMed Web of Science ®Google Scholar
• KURTZ TW, GARDNER DG: Transcription-modulating drugs: a new frontier in the treatment of essential hypertension. Hypertension (1998) 32:380–386.
   PubMed Web of Science ®Google Scholar
• •Good overview on PPAR-y-dependent gene transcription and the treatment of hypertension.
   Google Scholar
• LAKKA HM, LAAKSONEN DE, LAKKA TA etal.: The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. JAMA (2002) 288:2709–2716.
   Google Scholar
• LEHMANN JM, MOORE LB, SMITH-OLIVER TA, WILKISON WO, WILLS ON TM, KLIEWER SA: An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor-y (PPARy). Bia. Chem. (1995) 270:12953–12956.
   PubMed Web of Science ®Google Scholar
• ••First report identifying PPAR-y as theintracellular high affinity TZD receptor.
   Google Scholar
• KOEFFLER HP. PPARy and cancers. Clin. Cancer Res. (2003) 9:1–9.
   PubMed Web of Science ®Google Scholar
• PANIGRAHY D, SHEN LQ, KIERAN MW, KAIPAINEN A: Therapeutic potential of thiazolidinediones as anticancer agents. Expert Opirt. Investig. Drugs (2003) 12:1925–1237.
   PubMed Web of Science ®Google Scholar
• ELBRECHT A, CHEN Y, CULLINAN CA et al.: Molecular cloning, expression and characterization of human PPARs yl and y2. Biochem. Biophys. Res. Commun. (1996) 224:431–437.
   PubMed Web of Science ®Google Scholar
• VIDAL-PUIG AJ, CONSIDINE RV, JIMENEZ-LINAN M et al: PPAR gene expression in human tissues. Effects of obesity, weight loss, and regulation by insulin and glucocorticoids. j Ohl Invest. (1997) 99:2416–2422.
   Google Scholar
• FAJAS L, AUBOEUF D, RASPE E, SCHOONJANS K et al: The organization, promoter analysis, and expression of the human PPARy gene. J. Biol. Chem. (1997) 272:18779–18789.
   PubMed Web of Science ®Google Scholar
• •Good paper on variability of PPAR-y expression in humans.
   Google Scholar
• GUAN Y, ZHANG Y, DAVIS L, BREYER MD: Expression of PPARs in urinary tract of rabbits and humans. Am. J. Physiol (1997) 273:F1013–F1022.
   PubMed Web of Science ®Google Scholar
• ELLIS CN, VARANI J, FISHER GJ et al: Troglitazone improves psoriasis and normalizes models of proliferative skin disease: Ligands for PPARy inhibit keratinocyte proliferation. Arch. Dermatol (2000) 136:609–616.
   PubMed Web of Science ®Google Scholar
• ••First demonstration of a therapeutic effectof a TZD on psoriasis in non-diabetic subjects and demonstration of PPAR-y expression in keratinocytes.
   Google Scholar
• DESVERGNE B, WAHLI W: PPARs: nuclear control of metabolism. Endocr. Rev (1999) 20:649–688.
   PubMed Web of Science ®Google Scholar
• RICOTE M, LI AC, WILLSON TM, KELLY CJ, GLASS CK. The PPARy is a negative regulator of macrophage activation. Nature (1998) 391:79–82.
   Google Scholar
• BENSON S, WU J, PADMANABHAN S, KURTZ TW, PERSHADSINGH HA: PPARy expression in human vascular smooth muscle cells: inhibition of growth, migration, and c-fos expression by the PPARy activator troglitazone. Am. J. Hyperterts. (2000) 13(1):74–82.
   PubMed Web of Science ®Google Scholar
• INOUE I, HAYASHI K, YAGASAKI F etal.: Apoptosis of endothelial cells may be mediated by genes of PPARyl and PPARa genes. J. Atheroscler. Thromb. (2003) 10:99–108.
   Google Scholar
• MUKHERJEE R, JOWL, CROSTON GE, PATERNITI JR: Identification, characterization, and tissue distribution of human PPAR isoforms PPAR72 versus PPARyl and activation with retinoid X receptor agonists and antagonists. J. Biol. Chem. (1997) 272:8071–8076.
   PubMed Web of Science ®Google Scholar
• •Good paper on the diversity of PPAR-y1 and -72 expression in human tissue.
   Google Scholar
• MUELLER E, DRORI S, AIYER A etal.: Genetic analysis of adipogenesis through PPARy isoforms. J. Biol. Chem. (2002) 277:41925–41930.
   Google Scholar
• KINTSCHER U, WAKINO S, BRUEMMER D et al: TGF-I3(1) induces PPARyl and y2 expression in human THP-1 monocytes. Biochem. Biophys. Res. Commun. (2002) 297:794–799.
   PubMed Web of Science ®Google Scholar
• MINOKOSHI Y, KAHN CR, KAHN BB: Tissue-specific ablation of the GLUT4 glucose transporter or the insulin receptor challenges assumptions about insulin action and glucose homeostasis. J. Biol. Chem. (2003) 278:33609–33612.
   PubMed Web of Science ®Google Scholar
• HEVENER AL, HEW, BARAK Y et al.: Muscle-specific PPARy deletion causes insulin resistance. Nat. Med. (2003) 9:1491–1497.
   PubMed Web of Science ®Google Scholar
• ••Excellent work demonstrating theimportance of PPAR-y in skeletal muscle relative to adipose tissue by utilising tissue-specific knockout models.
   Google Scholar
• WATKINS PB, WHITCOMB RW: Hepatic dysfunction associated with troglitazone. N Engl. J. Med. (1998) 338:916–917.
   PubMed Web of Science ®Google Scholar
• LEBOVITZ HE. Differentiating membersof the thiazolidinedione class: a focus on safety. Diabetes Metab. Res. Rev (2002) 18:S23–S29.
   PubMed Web of Science ®Google Scholar
• MUDALIAR S, CHANG AR, HENRY RR: Thiazolidinediones, peripheral edema, and Type 2 diabetes: incidence, pathophysiology, and clinical implications. Endocr. Pict. (2003) 9:406–416.
   PubMedGoogle Scholar
• DELEA TE, EDELSBERG JS, HAGIWARA M, OSTER G, PHILLIPS LS: Use of thiazolidinediones and risk of heart failure in people with Type 2 diabetes: a retrospective cohort study. Diabetes Care. (2003) 26:2983–2989.
   PubMed Web of Science ®Google Scholar
• •First large comprehensive study on the incidence of heart failure in Type 2 diabetics treated with TZDs.
   Google Scholar
• SKRUMSAGER BK, NIELSEN la, MULLER M, PABST G, DRAKE PG, EDSBERG B: Ragaglitazar: the pharmacokinetics, pharmacodynamics, and tolerability of a novel dual PPARa and y agonist in healthy subjects and patients with Type 2 diabetes. J. Chu. Pharmacol (2003) 43:1244–1256.
   Google Scholar
• CARDILLO C, NAMBI S, KILCOYNE C et al.: Insulin stimulates both endothelin and nitric oxide activity in the human forearm. Circulation (1999) 100:820–825.
   PubMed Web of Science ®Google Scholar
• SATOH H, TSUKAMOTO K, HASHIMOTO Y etal.: Thiazolidinediones suppress endothelin-1 secretion from bovine vascular endothelial cells: A new possible role of PPARy on vascular endothelial function. Biochem. Biophys. Res. Commun. (1999) 254:757–763.
   Google Scholar
• GHAZZI MN, PEREZ JE, ANTONUCCI TK et al.: Cardiac and glycemic benefits of troglitazone treatment in NIDDM. The Troglitazone Study Group. Diabetes (1997) 46:433–439.
   Google Scholar
• ST JOHN SUTTON M, RENDELL M, DANDONA P et al: A comparison of the effects of rosiglitazone and glyburide on cardiovascular function and glycemic control in patients with Type 2 diabetes. Diabetes Care. (2002) 25:2058–2064.
   PubMed Web of Science ®Google Scholar
• PRESCRIBING INFORMATION: ACTOS® (pioglitazone hydrochloride) Tablets, Takeda Chemical Industries Ltd, Osaka, Japan.
   Google Scholar
• PRESCRIBING INFORMATION: Avandia® (rosiglitazone maleate) Tablets, SmithKline Beecham Pharmaceuticals, Philadelphia, PA, USA.
   Google Scholar
• MONTAGUE CT, O'RAHILLY S: The perils of portliness: causes and consequences of visceral adiposity. Diabetes (2000) 49:883–888.
   PubMed Web of Science ®Google Scholar
• PERSHADSINGH HA, BENSON SC, HO CI, KURTZ TW: Identification of PPARy activators that do not promote fluid retention and edema: implications for treating insulin resistant hypertension and the metabolic syndrome. Proceedings, Symposium on the Role of Nuclear Receptors in Cardiovascular Disease. (2003), San Diego, CA, USA (Abstract).
   Google Scholar
• BENSON SC, PERSHADSINGH HA, HO CI etal.: Identification of telmisartan as a unique angiotensin II receptor antagonist with selective PPARy modulating activity. Hypertension (2004) (In press).
   Google Scholar
• WHITE M, RACINE N, DUCHARME A, DE CHAMPLAIN J: Therapeutic potential of angiotensin II receptor antagonists. Expert Opin. Investig. Drugs (2001) 10:1687–1701.
   PubMed Web of Science ®Google Scholar
• LINDHOLM LH, IBSEN H, BORCH-JOHNSEN K et al: Risk of new-onset diabetes in the Losartan Intervention For Endpoint reduction in hypertension study. J. Hypertens. (2002) 20:1879–1886.
   PubMed Web of Science ®Google Scholar
• JANKE J, ENGELI S, GORZELNIAK K, LUFT FC, SHARMA AM: Mature adipocytes inhibit in vitro differentiation of human preadipocytes via angiotensin Type 1 receptors. Diabetes (2002) 51: 1699-1707.
   Google Scholar
• SHARMA AM, JANKE J, GORZELNIAK K, ENGELI S, LUFT FC: Angiotensin blockade prevents Type 2 diabetes by formation of fat cells. Hypertension (2002) 40:609–611.
   PubMed Web of Science ®Google Scholar
• HENRIKSEN EJ, JACOB S, KINNICK TR, TEACHEY MK, KREKLER M: Selective angiotensin II receptor antagonism reduces insulin resistance in obese Zucker rats. Hypertension (2001) 38:884–890.
   PubMed Web of Science ®Google Scholar
• DIAMANT M, HEINE RJ: TZDs in Type 2 diabetes mellitus: current clinical evidence. Drugs (2003) 63:1373–1405.
   PubMed Web of Science ®Google Scholar
• NARCE M, POISSON JP: Novel PPARy dependent and independent effects for thiazolidinediones. Cum: Opin. (2003) 14:651–652.
   Web of Science ®Google Scholar
• CHO DH, CHOI YJ, JO SA, JO I: Nitric oxide production and regulation of endothelial nitric oxide synthase phosphorylation by prolonged treatment with troglitazone: Evidence for involvement of PPARy dependent and PPARy independent signaling pathways. J. Biol. Chem. (2003) 279(4):2499–2506.
   PubMed Web of Science ®Google Scholar
• HILDING A, HALL K, SKOGSBERG J et al: Troglitazone stimulates IGF-binding protein-1 by a PPARy independent mechanism. Biochem. Biophys. Res. Commun. (2003) 303:693–699.
   PubMed Web of Science ®Google Scholar
• CHEN E WANG M, O'CONNOR JP, HE M, TRIPATHI T, HARRISON LE: Phosphorylation of PPARy via active ERK1/2 leads to its physical association with p65 and inhibition of NF-icB. J. Cell. Biochem. (2003) 90:732–744.
   PubMed Web of Science ®Google Scholar
• GELMAN L, FRUCHART JC, AUWERX J: An update on the mechanisms of action of the PPARs and their roles in inflammation and cancer. Cell. Ma] Life Li. (1999) 55:932–943.
   PubMed Web of Science ®Google Scholar
• CLARK RB: The role of PPARs in inflammation and immunity. J. Leukoc. Biol. (2002) 71:388–400.
   PubMed Web of Science ®Google Scholar
• •Good review on the immunomodulatory roles of PPAR-y and PPAR-a.
   Google Scholar
• BLANQUART C, BARBIER 0, FRUCHART JC, STAELS B, GLINEUR C: PPARs: regulation of transcriptional activities and roles in inflammation. J. Steroid Biochem. Mol. Biol. (2003) 85:267–273.
   PubMed Web of Science ®Google Scholar
• ZIMMET P, ALBERTI KG, SHAW J: Global and societal implications of the diabetes epidemic. Nature (2001) 414:782–787.
   PubMed Web of Science ®Google Scholar
• LAKKA HM, LAAKSONEN DE, LAKKA TA et al: The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. JAMA (2002) 288:2709–2716.
   PubMed Web of Science ®Google Scholar
• PARK YW, ZHU S, PALANIAPPAN L, HESHKA S, CARNETHON MR, HEYMSFIELD SB: The metabolic syndrome: prevalence and associated risk factor findings in the US population from the Third National Health and Nutrition Examination Survey, 1988-1994. Arch. Intern. Med. (2003) 163:427–436.
   PubMed Web of Science ®Google Scholar
• LAAKSONEN DE, LAKKA HM, NISKANEN LK, KAPLAN GA, SALONEN JT, LAKKA TA: Metabolic syndrome and development of diabetes mellitus: application and validation of recently suggested definitions of the metabolic syndrome in a prospective cohort study. Am. J. Epidemiol. (2002) 156:1070–1077.
   PubMed Web of Science ®Google Scholar
• HAFFNER SM, GREENBERG AS, WESTON WM, CHEN H, WILLIAMS K, FREED MI: Effect of rosiglitazone treatment on nontraditional markers of cardiovascular disease in patients with Type 2 diabetes mellitus. Circulation (2002) 106:679–684.
   PubMed Web of Science ®Google Scholar
• Executive Summary of The Third Report ofThe National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA (2001) 285:2486–2497.
   PubMed Web of Science ®Google Scholar
• MOLLER DE: New drug targets for Type 2 diabetes and the metabolic syndrome. Nature (2001) 414:821–827.
   PubMed Web of Science ®Google Scholar
• MARTENS FM, VISSEREN FL, LEMAY J, DE KONING EJ, RABELINK TJ: Metabolic and additional vascular effects of thiazolidinediones. Drugs (2002) 62:1463–1480.
   PubMed Web of Science ®Google Scholar
• BOYLE PJ, KING AB, OLANSKY L et al: Effects of pioglitazone and rosiglitazone on blood lipid levels and glycemic control in patients with Type 2 diabetes mellitus: a retrospective review of randomly selected
   Google Scholar
• NASS CM, BLUMENTHAL RS: Glitazones and the potential improvement of lipid profiles in diabetes patients at high risk for cardiovascular disease. Am. Marrag. Care (2000) 6:S1247–S1256.
   PubMed Web of Science ®Google Scholar
• WALCZAK R, TONTONOZ P: PPARadigms and PPARadoxes: expanding roles for PPARy in the control of lipid metabolism. j Lipid Res. (2002) 43:177–186.
   PubMed Web of Science ®Google Scholar
• BONORA E, FORMENTINI G, CALCATERRA F et al.: HOMA-estimated insulin resistance is an independent predictor of cardiovascular disease in Type 2 diabetic subjects: prospective data from the Verona Diabetes Complications Study. Diabetes Care (2002) 25:1135–1141.
   PubMed Web of Science ®Google Scholar
• LYONS TJ: Glycation and oxidation: a rolein the pathogenesis of atherosclerosis. Am. Cardiol (1993) 71:26B–31B.
   Google Scholar
• MATSUZAWA Y, FUNAHASHI T, KIHARA S, SHIMOMURA I: Adiponectin and metabolic syndrome. Arterioscler. Thromb. Vase. Biol. (2004) 24(1):29–33.
   PubMed Web of Science ®Google Scholar
• OUCHI N, KIHARA S, FUNAHASHI T, MATSUZAWA Y, WALSH K: Obesity, adiponectin and vascular inflammatory disease. Cure Opin. Lipidol (2003) 14:561–566.
   PubMed Web of Science ®Google Scholar
• SHAND BI, SCOTT RS, ELDER PA, GEORGE PM: Plasma adiponectin in overweight, nondiabetic individuals with or without insulin resistance. Diabetes Obes. Metab. (2003) 5:349–353.
   PubMed Web of Science ®Google Scholar
• YAMAMOTO Y, HIROSE H, SAITO I et al.: Correlation of the adipocyte-derived protein adiponectin with insulin resistance index and serum high-density lipoprotein-cholesterol, independent of body mass index, in the Japanese population. Clin. Sci. (Lmid) (2002) 103:137–142.
   PubMed Web of Science ®Google Scholar
• SATOH N, OGAWA Y, USUI T et al: Antiatherogenic effect of pioglitazone in Type 2 diabetic patients irrespective of the responsiveness to its antidiabetic effect. Diabetes Care (2003) 26:2493–2499.
   PubMed Web of Science ®Google Scholar
• YANG WS, JENG CY, WU TJ etal.: Synthetic PPARy agonist, rosiglitazone, increases plasma levels of adiponectin in Type 2 diabetic patients. Diabetes Care (2002) 25:376–380.
   Google Scholar
• GUSTAFSON B, JACK MM, CUSHMAN SW, SMITH U: Adiponectin gene activation by thiazolidinediones requires PPAR72, but not C/EBP a-evidence for differential regulation of the aP2 and adiponectin genes. Biochem. Biophys. Res. Commun. (2003) 308:933–939.
   PubMed Web of Science ®Google Scholar
• FULLERT S, SCHNEIDER E HAAK E etal.: Effects of pioglitazone in nondiabetic patients with arterial hypertension: a double-blind, placebo-controlled study. j Clin. Endocrinol Metab. (2002) 87:5503–5506.
   Google Scholar
• •First study to show a blood pressure-lowering effect of a TZD in non-diabetic subjects.
   Google Scholar
• RAJI A, SEELY EW, BEKINS SA, WILLIAMS GH, SIMONSON DC: Rosiglitazone improves insulin sensitivity and lowers blood pressure in hypertensive patients. Diabetes Care (2003) 26:172–178.
   PubMed Web of Science ®Google Scholar
• ZHANG HY, REDDY SR, KOTCHEN TA: Antihypertensive effect of pioglitazone is not invariably associated with increased insulin sensitivity. Hypertension (1994) 24:106–110.
   PubMed Web of Science ®Google Scholar
• GARG R, KUMBKARNI Y, ALJADA A etal.: Troglitazone reduces reactive oxygen species generation by leukocytes and lipid peroxidation and improves flow-mediated vasodilatation in obese subjects. Hypertension (2000) 36:430–435.
   Google Scholar
• BUCHANAN TA, MEEHAN WP JENG YY et al.: Blood pressure lowering by pioglitazone. Evidence for a direct vascular effect. J OM. Invest. (1995) 96:354–360.
   Google Scholar
• BAKRIS G, VIBERTI G, WESTON WM,92.HEISE M, PORTER LE, FREED MI: Rosiglitazone reduces urinary albumin excretion in Type II diabetes. j Hum. Hypertens. (2003) 17:7–12.93.
   Google Scholar
• DANDONA P, ALJADA A, MOHANTY P et al: Insulin inhibits intranuclear nuclear factor-icB and stimulates IicB in mononuclear cells in obese subjects: evidence for an anti-inflammatory effect?I Endocrirrol Metab. (2001) 86:3257-3265.94.
   Google Scholar
• IIYAMA K, HAJRA L, IIYAMA M et al: Patterns of VCAM-1 and ICAM-1 expression in rabbit and mouse atherosclerotic lesions and at sites predisposed to lesion formation. Circ. Res. (1999) 85:199-207.95.
   Google Scholar
• ROBERTS AW, THOMAS A, REES A, EVANS M: PPARy agonists in atherosclerosis: current evidence and future
   Google Scholar
• ROSS R: Mechanisms of disease: Atherosclerosis: an inflammatory disease. N Engl. J. Med. (1999) 340:115–126.
   PubMed Web of Science ®Google Scholar
• NATALI A, BALDEWEG S, TOSCHI E et al.: Rosiglitazone directly improves endothelial function in Type 2 diabetic patients. Diabetes (2002) 51\(Suppl. 2):573 (Abstract).
   Google Scholar
• WINKLER K, KONRAD T, FULLERT S et al.: Pioglitazone reduces atherogenic dense LDL particles in nondiabetic patients with arterial hypertension: a double-blind, placebo-controlled study. Diabetes Care (2003) 26:2588–2594.
   PubMed Web of Science ®Google Scholar
• ••First clinical study to demonstrate anantiatherogenic effect in non-diabetic patients with hypertension, independent from lowering triglycerides.
   Google Scholar
• WINKLER K, ABLETSHAUSER C, HOFFMANN MM et al.: Effect of fluvastatin slow-release on low density lipoprotein (LDL) subfractions in patients with Type 2 diabetes mellitus: baseline LDL profile determines specific mode of action. j Clin. Endocrinol Metab. (2002) 87:5485-5490. DIEP QN, EL MABROUK M, COHN JS et al: Structure, endothelial function, cell growth, and inflammation in blood vessels of angiotensin II-infused rats: role of PPARy. Circulation (2002) 105:2296-2302. LI M, PASCUAL G, GLASS CK: PPARy dependent repression of the inducible nitric oxide synthase gene. Mal Cell. Biol. (2000) 20:4699-4707. HANSSON GK, JONASSON L, HOLM J, CLAESSON-WELSH L: Class II MHC antigen expression in the atherosclerotic plaque: smooth muscle cells express HLA-DR, HLA-DQ and the invariant y chain. Clin. Exp. Immurrol (1986) 64:261-268. KWAK BR, MYIT S, MULHAUPT F et al.: PPARy but not PPARa ligands are potent repressors of major histocompatibility complex class II induction in atheroma-associated cells. Circ. Res. (2002) 90:356–362.
   Google Scholar
• DIEP QN, EL MABROUK M, COHN JS et al: Structure, endothelial function, cell growth, and inflammation in blood vessels of angiotensin II-infused rats: role of PPARy. Circulation (2002) 105:2296–2302.
   PubMed Web of Science ®Google Scholar
• LI M, PASCUAL G, GLASS CK: PPARy dependent repression of the inducible nitric oxide synthase gene. Mol Cell. Biol. (2000) 20:4699–4707.
   PubMed Web of Science ®Google Scholar
• HANSSON GK, JONASSON L, HOLM J, CLAESSON-WELSH L: Class II MHC antigen expression in the atherosclerotic plaque: smooth muscle cells express HLA-DR, HLA-DQ and the invariant y chain. Clin. Exp. Immunol (1986) 64:261–268medical records. Clin. Thee (2002) 24:378–396.
   PubMed Web of Science ®Google Scholar
• •Good study demonstrating the beneficial effect of a TZD on vascular function in non-diabetics. directions. Curr. Opin. Lipidol (2003) 14:567-573. Excellent review of the basic science and clinical data on the antiatherosclerotic effects of TZDs.
   Google Scholar
• KOSHIYAMA H, SHIMONO D, KUWAMURA N, MINAMIKAWA J, NAKAMURA Y: Inhibitory effect of pioglitazone on carotid arterial wall thickness in Type 2 diabetes. J. Clin. Endocrinol. Metab. (2001) 86:3452-3456. First demonstration that a TZD ameliorates atherosclerosis in Type 2 diabetics.
   Google Scholar
• STAKOS DA, SCHUSTER DP, SPARKS EA, WOOLEY CF, OSEI K, BOUDOULAS H: Long-term cardiovascular effects of insulin sensitizer troglitazone on non-diabetic individuals with insulin resistance: double blind, prospective randomized study. J. Cardiol (2003) 41:183–190.
   PubMedGoogle Scholar
• •Good clinical demonstration that a TZD improves vascular function in non-diabetic, insulin resistant patients.
   Google Scholar
• MARX N, FROEHLICH J, SIAM L et al: Antidiabetic PPARy activator rosiglitazone reduces MIV1P-9 serum levels in Type 2 diabetic patients with coronary artery disease. Arterioscler. Thromb. Vase. Biol. (2003) 23:283–288.
   PubMed Web of Science ®Google Scholar
• SCHONBECK U, LIBBY P: CD40 signaling and plaque instability. Circ. Res. (2001) 89:1092–1103.
   PubMed Web of Science ®Google Scholar
• MARX N, IMHOF A, FROEHLICH J et al.: Effect of rosiglitazone treatment on soluble CD4OL in patients with Type 2 diabetes and coronary artery disease. Circulation (2003) 107: 1954-1957.
   Google Scholar
• SPOELSTRA-DE MAN AM, BROUWER CB, STEHOUWER CD, SMULDERS YM: Rapid progression of albumin excretion is an independent predictor of cardiovascular mortality in patients with Type 2 diabetes and microalbuminuria. Diabetes Care (2001) 24:2097–2101.
   PubMed Web of Science ®Google Scholar
• BAKRIS G, VIBERTI G, WESTON WM, HEISE M, PORTER LE, FREED MI: Rosiglitazone reduces urinary albumin excretion in Type II diabetes. J. Hum. Hypertens. (2003) 17:7–12.
   PubMed Web of Science ®Google Scholar
• NAKAMURA T, USHIYAMA C, OSADA S, HARA M, SHIMADA N, KOIDE H: Pioglitazone reduces urinary podocyte excretion in Type 2 diabetes patients with microalbuminuria. Metabolism (2001) 50:1193–1196.
   PubMed Web of Science ®Google Scholar
• TAKAGI T, AKASAKA T, YAMAMURO A et al.: Impact of insulin resistance on neointimal tissue proliferation after coronary stent implantation. Intravascular ultrasound studies. J. Diabetes Complications (2002) 16:50–55.
   PubMed Web of Science ®Google Scholar
• TAKAGI T, YAMAMURO A, TAMITA K et al.: Impact of troglitazone on coronary stent implantation using small stents in patients with Type 2 diabetes mellitus. Am. Cardiol (2002) 89:318–322.
   PubMed Web of Science ®Google Scholar
• CHOI SH, CHOI DH, KO YK etal.: Preventive effects of rosiglitazone on restenosis after coronary stenting in patients with Type 2 diabetes. Diabetes (2003) 52\(Suppl. 1) (Abstract).
   Google Scholar
• •First demonstration that rosiglitazone prevents coronary artery restenosis rates.
   Google Scholar
• TAKAGI T, YAMAMURO A, TAMITA K et al: Pioglitazone reduces neointimal tissue proliferation after coronary stent implantation in patients with Type 2 diabetes mellitus: an intravascular ultrasound scanning study. Am. Heart J. (2003) 146:E5 (Abstract).
   Google Scholar
• •First demonstration that pioglitazone prevents coronary artery restenosis.
   Google Scholar
• SHIOMI T, TSUTSUI H, HAYASHIDANI S et al: Pioglitazone, a PPARy agonist, attenuates left ventricular remodeling and failure after experimental myocardial infarction. Circulation (2002) 106:3126–3132.
   PubMed Web of Science ®Google Scholar
• •Good study demonstrating the cardioprotective effect of a TZD, implying a potential therapeutic benefit in heart failure.
   Google Scholar
• YUE TL, CHEN J, BAO W et al: In vivo myocardial protection from ischemia/ reperfusion injury by the PPARy agonist rosiglitazone. Circulation (2001) 104:2588–2594.
   PubMed Web of Science ®Google Scholar
• •Good study demonstrating the cardioprotective effect of a TZD.
   Google Scholar
• WAYMAN NS, HATTORI Y, McDONALD MC et al: Ligands of PPARy and PPARa reduce myocardial infarct size. FASEB J. (2002) 16:1027–1040.
   PubMed Web of Science ®Google Scholar
• IGLARZ M, TOUYZ RM, VIEL EC et al: PPARa and y activators prevent cardiac fibrosis in mineralocorticoid-dependent hypertension. Hypertension (2003) 42:737–743.
   PubMedGoogle Scholar
• YANG XY, WANG LH, CHEN T et al: Activation of human T lymphocytes is inhibited by PPARy agonists. PPARy co-association with transcription factor NFAT. J. Biol. Chem. (2000) 275:4541–4544.
   Google Scholar
• ••Excellent basic science work demonstratingthat PPAR-y suppresses T-lymphocyte activation, binding directly to NFAT and preventing it from binding to its cognate DNA-binding domain.
   Google Scholar
• KEEGAN BM, NOSEWORTHY JH: Multiple sclerosis. Ann. Rev Med. (2002) 53:285–302.
   PubMed Web of Science ®Google Scholar
• FEINSTEIN DL, GALEA E, GAVRILYUK V etal.: PPARy agonists prevent experimental autoimmune encephalomyelitis. Ann. Neural. (2002) 51:694–702.
   Google Scholar
• NIINO M, IWABUCHI K, KIKUCHI S etal.: Amelioration of experimental autoimmune encephalomyelitis in C57BL/6 mice by an agonist of PPARy. Neuroimmunol (2001) 116:40–48.
   Google Scholar
• •First demonstration of a therapeutic effect of a TZD in experimental autoimmune encephalomyelitis.
   Google Scholar
• BRIGHT, JJ, NATARAJAN C, MUTHIAN G, BARAK Y, EVANS RM: PPARy-deficient heterozygous mice develop an exacerbated neural antigen-induced Thl response and experimental allergic encephalomyelitis. J. hiimuriol. (2003) 171:5743–5750.
   Google Scholar
• •Good basic science study showing that experimental allergic encephalomyelitis is associated with PPAR-y deficiency.
   Google Scholar
• PERSHADSINGH HA, SCHMIDT S, HENEKA MT et al: Pioglitazone treatment in a patient with chronic progressive multiple sclerosis. 2nd International Symposium on PPARs: From Basic Science to Clinical Applications. (2003) Florence, Italy (Abstract).
   Google Scholar
• PERSHADSINGH HA, SPROUL JA, BENJAMIN E, FINNEGAN J, AMIN NM: Treatment of psoriasis with troglitazone therapy. Arch. Dermatol. (1998) 134:1304–1305.
   PubMed Web of Science ®Google Scholar
• •First demonstration of a therapeutic effect of a TZD in psoriasis.
   Google Scholar
• MALHOTRA S, SHAFIQ P, PANDHI P, KUMAR B, JAIN R, AGGARWAL M: Pioglitazone versus placebo in patients with plaque psoriasis: Pilot trial study design and preliminary results. 31st Annual Meeting American Coll. Chia. Pharmacol. (2002) San Francisco, CA, USA (Abstract).
   Google Scholar
• PERSHADSINGH HA, VENKATRAMAN M, CHITTIBOYINA A et al: Novel PPARy ligands for topical treatment of inflammatory and proliferative diseases of skin. 2nd International Symposium on PPARs: From Basic Science to Clinical Applications. (March 19–22, 2003), Florence, Italy, p44 (Abstract).
   Google Scholar
• •First demonstration of a beneficial effect of a TZD in an animal model of atopic dermatitis.
   Google Scholar
• HASHIMOTO Y, NAKAHARA K: Improvement of asthma after administration of pioglitazone. Diabetes Care. (2002) 25:401.
   PubMed Web of Science ®Google Scholar
• •First demonstration of a therapeutic effect of a TZD in asthma.
   Google Scholar
• RAY A, COHN L: Th2 cells and GATA-3 in asthma: new insights into the regulation of airway inflammation. I Clin. Invest. (1999) 104:985–993.
   PubMed Web of Science ®Google Scholar
• WOERLY G, HONDA K, LOYENS M et al: PPARa and y down-regulate allergic inflammation and eosinophil activation. J. Exp. Med. (2003) 198:411–421.
   PubMed Web of Science ®Google Scholar
• DUBUQUOY L, JANSSON EA, DEEB S et al.: Impaired expression of PPARy in ulcerative colitis. Gastroenterology (2003) 124:1265–1276.
   PubMed Web of Science ®Google Scholar
• •Good study showing that PPAR-y is impaired in UC.
   Google Scholar
• SAUBERMANN LJ, NAKAJIMA A, WADA K et al.: PPARy agonist ligands stimulate a Th2 cytokine response and prevent acute colitis. Inllamm. Bowel Dis. (2002) 8:330–339.
   PubMed Web of Science ®Google Scholar
• LEWIS JD, LICHTENSTEIN GR, STEIN RB et al.: An open-label trial of the PPARy ligand rosiglitazone for active ulcerative colitis. Am. j Gastroenterol (2001) 96:3323–3328.
   PubMed Web of Science ®Google Scholar
• •First demonstration of a therapeutic effect of a TZD on ulcerative colitis in non-diabetic subjects.
   Google Scholar
• DE GASPARO M, CATT KJ, INAGAMI T, WRIGHT JW, UNGER T: International union of pharmacology. XXIII. The angiotensin II receptors. Pharmacol Rev (2000) 52:415–472.
   PubMed Web of Science ®Google Scholar
• TOUYZ RM, BERRY C: Recent advances in angiotensin II signaling. Biz. I Med. Biol. Res. (2002) 35:1001–1015.
   PubMed Web of Science ®Google Scholar