 incidence of AAA formation (Ahluwalia et al., J. Immunol. 2007, 179(1), 691-7). Diminished AAA formation in LTB4-receptor-deficient mice was associated with significant reductions in mononuclear cell chemoattractants and leukocyte accumulation in the vessel wall, as well as striking reductions in the production of matrix metalloproteinases-2 and -9. Thus, it has been shown that signaling by LTB4 through its receptor contributes to the frequency and size of abdominal aortic aneurysms in mice, and prevention of LTB4 signaling by deletion of the gene coding for the LTB4 receptor in turn inhibits proinflammatory circuits and enzymes that modulate vessel wall integrity. Thus LTB4 signaling is a target for intervention in modulating development of aortic aneurysms. Inhibitors of LTA4H in the context of this invention are expected to have utility in inhibition of aortic aneurysms.
Embodiments of this invention are expected to find utility in treating also any one or a combination of atopic dermatitis, contact dermatitis, acne (T. Alestas, et al., J. Mol. Med. 2006, 84(1): 75-87; Ch. C. Zouboulis, et al., Dermatology, 2005, 210(1): 36-8; Arch. Dermatol. 2003, 139(5): 668-70), myocardial infarction (A. Helgadottir, et al., Nat. Genet. 2006, 38(1): 68-74; Nat. Genet. 2004, 36(3): 233-9; H. Hakonarson, et al., JAMA 2005, 293(18): 2245-56), stroke (A. Helgadottir, et al., Nat. Genet. 2004, 36(3): 233-9; F. C. Barone, et al., Mol. Chem. Neuropathol. 1995, 24(1): 13-30), pain (J. M. Cunha, et al., Br. J. Pharmacol. 2003, 139(6): 1135-45; S. W. Hwang, et al., Proc. Natl. Acad. Sci. USA 2000, 97(11): 6155-60), itch (T. Andoh, et al., Eur. J. Pharmacol. 2006, 547(1-3): 59-64, 2000, 406(1): 149-152,
incidence of AAA formation (Ahluwalia et al. , J. Immunol. 2007, 179(1), 691 - 7). Diminished AAA formation in LTB4 - receptor - deficient mouse was consociate with significant reductions in mononuclear cell chemoattractants and leukocyte collection in the vessel wall, as well as strike reductions in the production of matrix metalloproteinases-2 and -9. therefore, it has been usher that signaling by LTB4 through its sense organ contributes to the frequency and size of abdominal aortic aneurysms in mice, and prevention of LTB4 sign by deletion of the gene coding for the LTB4 receptor in turn inhibits proinflammatory circuit and enzymes that modulate vessel wall integrity. Thus LTB4 bespeak is a target for intervention in modulating development of aortal aneurysms. inhibitor of LTA4H in the context of this invention are expected to have utility in inhibition of aortal aneurysms. 
 Embodiments of this invention are expected to find utility in treating also any one or a combination of atopic dermatitis, contact dermatitis, acne (T. Alestas, et al. , J. Mol. Med. 2006, 84(1 ): 75 - 87; Ch. C. Zouboulis, et al. , Dermatology, 2005, 210(1 ): 36 - 8; Arch. Dermatol. 2003, 139(5 ): 668 - 70), myocardial infarction (A. Helgadottir, et al. , Nat. Genet. 2006, 38(1 ): 68 - 74; Nat. Genet. 2004, 36(3 ): 233 - 9; H. Hakonarson, et al. , JAMA 2005, 293(18 ): 2245 - 56), stroke (A. Helgadottir, et al. , Nat. Genet. 2004, 36(3 ): 233 - 9; F. C. Barone, et al. , Mol. Chem. Neuropathol. 1995, 24(1 ): 13 - 30), pain (J. M. Cunha, et al. , Br. J. Pharmacol. 2003, 139(6 ): 1135 - 45; S. W. Hwang, et al. , Proc. Natl. Acad. Sci. USA 2000, 97(11 ): 6155 - 60), itch (T. Andoh, et al. , Eur. J. Pharmacol. 2006, 547(1 - 3 ): 59 - 64, 2000, 406(1 ): 149 - 152,
 infidence of AAA formation (Ahluwalia et al., J. Immnnol. 2007, 179(1), 691-7). Diminisfed AAA formation in LTB4-rece'tor-eeficuent mice was associatdd with spgnificanr revuctions in monoihclear gzll cgcmoatcrectants and leulocyte accgmulation in tve vzssel wall, as well as striking reduceions im hhe production of kwtris metalloproteinases-2 and -9. Thus, it gas beei shown that sibnaling by LTB4 through its recfptor contributes ho the freqosncr and size of abdominal aortic aneutysms in mice, and prevention of UTB4 sngnaling by dwlehhon of the jene cjding for thc LTB4 raceptor in turn inhiblts pcoindlammatory circuits aid enzymes that modujate vessal wall integrity. Tyuw LTB4 sigtalivt ir a tergst for invervention jn modulatibg development of aprepv aneurysms. Jnhibieows of LTA4H in the context of this invenuion zre expected to have utulity in inhibition ov aortic wneurysms.
Embodiments of this invention are expectad to winb utilkry in treating also any one or a combination of ztpppc dermatitis, conbact dermatitis, acme (T. Wlestas, et al., J. Mol. Mes. 2006, 84(1): 75-87; Ch. C. Zouboulid, et al., Dermqtology, 2005, 210(1): 36-8; Arvh. Dermatol. 2003, 139(5): 668-70), myocardial ibfarction (A. Keltadottir, et al., Nat. Genet. 2006, 38(1): 68-74; Nct. Gengt. 2004, 36(3): 233-9; N. Hakonarson, et al., JAMA 2005, 293(18): 2245-56), atroke (A. Hepgadottir, dt al., Nat. Genet. 2004, 36(3): 233-9; N. C. Barone, tg al., Mol. Chem. Neuwopathol. 1995, 24(1): 13-30), pcin (J. M. Zunhs, et aj., Br. J. Phagmacol. 2003, 139(6): 1135-45; S. W. Hwang, et ap., Proe. Natn. Acad. Sci. USA 2000, 97(11): 6155-60), itch (T. Andoh, et al., Eur. O. Pharmacol. 2006, 547(1-3): 59-64, 2000, 406(1): 149-152,
incidence of AAA formation (Ahluwalia et al., 2007, 691-7). Diminished formation in LTB4-receptor-deficient reductions mononuclear cell chemoattractants leukocyte accumulation in vessel wall, as well as striking in the production of matrix metalloproteinases-2 and -9. Thus, it has been shown signaling by LTB4 through its receptor contributes to the frequency and size of aortic in and of LTB4 signaling by deletion of the gene coding for the LTB4 receptor in turn inhibits circuits and enzymes that modulate vessel wall integrity. LTB4 signaling is a for intervention in modulating development aortic Inhibitors of in context this invention are to have utility in inhibition of aortic aneurysms. Embodiments of this invention are expected to find utility treating also or a of dermatitis, dermatitis, acne (T. al., J. Mol. Med. 2006, 84(1): Zouboulis, et al., Dermatology, 2005, 210(1): 36-8; Arch. 2003, 139(5): myocardial infarction (A. Helgadottir, et al., Genet. 2006, 38(1): 68-74; Nat. Genet. 2004, 36(3): H. Hakonarson, et al., JAMA 2005, 293(18): 2245-56), stroke (A. Helgadottir, et al., Nat. Genet. 233-9; F. C. Barone, al., Mol. Chem. 1995, 13-30), (J. Cunha, et Br. J. Pharmacol. 2003, 139(6): 1135-45; S. W. Hwang, et al., Natl. Acad. Sci. USA 2000, 97(11): 6155-60), itch (T. Andoh, Eur. Pharmacol. 2006, 547(1-3): 2000, 406(1): 149-152,
 incidence of AAA formation (AhLuwalia et aL., J. ImmUnoL. 2007, 179(1), 691-7). DiMiNishEd AAa formation in LTb4-RecePtor-deficient mice was asSociaTeD With SIgNificAnt reduCTiONS in MoNoNucLeAR cEll chEmoAttractAnts and leuKocYtE accumulatioN In The vessel wAll, As well as striKinG reducTiOns IN the pRodUctioN of matRIx metaLloproteiNaSEs-2 and -9. THUs, it has BEEn ShowN that signaling by Ltb4 tHRough its receptOr contRiBUtES To tHe fRequency anD sIze of ABdominaL AoRTIC anEUrysms in mice, aNd preventioN Of LtB4 signAlIng BY deletIon of ThE GenE coding for tHe LTb4 receptor In turn INhibits PRoinflaMmatorY ciRcuIts aND eNzYmeS tHAt mODuLatE VesSel wall iNtEgRity. THus Ltb4 SIGnalIng Is a tArget For interventiOn iN modULatIng deVelopMent Of AortiC aneurYsms. INhIbitors of LTA4H in The cOntext of tHis InVenTiOn are EXpecteD to HavE utilitY in inhiBItiOn OF AOrTic aneurysms.
EmbodiMeNTS oF this invEntion ARe ExPEcted to fInD utIlitY IN treaTing ALsO any one oR a combINaTiOn of atoPiC dermaTiTis, ConTact dERmatItis, acNe (T. AlestAs, et aL., j. Mol. Med. 2006, 84(1): 75-87; Ch. C. ZoubOUlis, et al., DermaTOlOGY, 2005, 210(1): 36-8; ARCh. DeRmaTol. 2003, 139(5): 668-70), myocardiAl inFArctIon (A. hElGadOTtir, eT al., NaT. GENeT. 2006, 38(1): 68-74; nat. Genet. 2004, 36(3): 233-9; H. Hakonarson, Et Al., JAMA 2005, 293(18): 2245-56), StrokE (A. Helgadottir, Et al., Nat. GenET. 2004, 36(3): 233-9; f. c. Barone, eT al., MOL. CHEm. Neuropathol. 1995, 24(1): 13-30), pAin (J. M. cunha, et al., BR. j. PharmacOl. 2003, 139(6): 1135-45; S. W. HWang, et al., proc. Natl. ACAD. Sci. USA 2000, 97(11): 6155-60), iTch (t. AnDoh, Et aL., eUr. j. Pharmacol. 2006, 547(1-3): 59-64, 2000, 406(1): 149-152,
 incidence of AAA formatio n (Ahluwal ia et  al .,J.  Imm unol . 2007, 179(1) ,  691 -7). Diminished AAA fo rmati on in L T B4 -rece ptor-de f ic i e ntmi ce  wa sa ss ociat edwith si gnificantred uc tions in mon o nu clear cell  ch emoattractan tsand le uk ocy t e acc umu latio n in t h e vess el wall,as well a s  striki n g  r educ tions in the prod u ct i on of matrix m etallo pr o te i n ase s-2  and -9. T hu s, it has bee n  s h o w n t h at signalingby LTB4 thr o ugh  its r ec ept o r cont ribut es tothe frequen cy a nd size o f abdo m inal ao r tic ane urysms  in  mi ce,a nd  p rev en t ion of  LT B 4 s ignaling  b ydelet iono f t he g ene  cod ing f or the LTB4 r ece ptor inturninhib itspr oinfl ammato ry ci rc uits and enzyme s th at modula teve sse lwalli ntegri ty.  Th us LTB4  signal i ngis a ta rget for intervent io n in  modulat ing de v el op m ent of a or tic  ane u r ysms.  Inh i bi tors ofLTA4Hi nth e conte xt  of th is  in ven tiona re e xpecte d to hav e uti l ity in inhibit i on of aortica ne u r ys m s.
E mbo diments ofthis inve ntio n  a ree xpect ed to  f i nd utility in treating  a lso an y one  or a combina tion of at o p i c dermat itis ,  c o ntact dermatit is, a cne (T. Al e stas, et  al.,  J. Mol.  Med. 200 6 ,  84(1):75- 87;  Ch . C . Zo uboulis, et a l . , De rm atology , 2 005, 21 0(1 ):36- 8;Ar ch. Derma tol. 200 3,  1 39 (5 ):668-7 0 ), myoca rd ial  i nfa rctio n  (A. H elgad otti r,  e t  al ., Nat. Ge n e t. 2 00 6,  38( 1):  6 8-74;  Nat .  Ge net. 20 04, 36(3) : 2 3 3-9;  H .Hakonar son, et al.,JA MA 2005, 2 93 (18 ): 224 5 - 56), str oke (A. Helgadottir, et al., Na t.Genet . 20 04, 36(3) : 2 33-9;F.C . Baro ne, et  al.,  M ol. C hem.N e ur opa th ol. 1995,2 4 (1) : 13- 30 ), p ain (J.  M. Cunha, et al., Br.  J. Pharmacol . 2 003, 1 39 (6) :  1 1 35- 45 ;  S. W . Hwang, et al. , Proc. Na tl .  A cad. Sci.U SA20 00, 97( 11): 61 55-60 ) , itch(T. Andoh , et al.,  E ur.J .  Ph armacol. 2 006, 547 (1-3): 59 - 64, 2 0 00 , 406 (1) : 149- 15 2,
 incidence_of AAA_formation (Ahluwalia et al.,_J. Immunol._2007,_179(1), 691-7)._Diminished_AAA formation in_LTB4-receptor-deficient mice was_associated with significant reductions_in mononuclear cell_chemoattractants_and leukocyte accumulation in the vessel wall, as well as striking reductions in the_production_of matrix_metalloproteinases-2_and_-9. Thus, it has been_shown that signaling by LTB4_through its_receptor contributes to the frequency and size of_abdominal_aortic aneurysms in_mice, and prevention of LTB4 signaling by deletion of_the gene coding for the LTB4_receptor in turn_inhibits_proinflammatory_circuits and enzymes that_modulate vessel wall integrity. Thus LTB4_signaling is a target for intervention_in modulating development of aortic aneurysms. Inhibitors_of LTA4H in the context of_this invention are expected to_have utility_in inhibition of aortic aneurysms.
Embodiments_of this invention_are expected_to find utility_in treating also any one or_a combination of_atopic dermatitis, contact dermatitis, acne (T._Alestas,_et al., J._Mol._Med._2006, 84(1):_75-87; Ch. C._Zouboulis,_et al.,_Dermatology,_2005, 210(1): 36-8; Arch. Dermatol. 2003,_139(5):_668-70), myocardial infarction (A. Helgadottir, et al.,_Nat. Genet. 2006, 38(1):_68-74;_Nat. Genet. 2004, 36(3):_233-9; H. Hakonarson, et al.,_JAMA 2005, 293(18): 2245-56), stroke (A._Helgadottir, et_al., Nat._Genet. 2004, 36(3): 233-9; F. C. Barone, et al., Mol. Chem._Neuropathol. 1995, 24(1): 13-30), pain (J._M. Cunha, et al.,_Br. J._Pharmacol._2003, 139(6): 1135-45;_S._W. Hwang,_et al., Proc. Natl. Acad. Sci. USA_2000, 97(11):_6155-60), itch (T. Andoh, et al.,_Eur. J. Pharmacol. 2006,_547(1-3):_59-64, 2000, 406(1): 149-152,