 pathological thrombus tends to form. As drugs for suppressing pathological thrombus formation, drugs for suppressing adhesion or aggregation of platelets, i.e., xe2x80x9cantiplatelet agentsxe2x80x9d, have attracted attention, and have found wide clinical use. The history of antiplatelet agents is relatively recent, and the development of better drugs of this type is expected.
As described above, the normal blood vessel is made highly antithrombotic by vascular endothelial cells. The roles of the vascular endothelial cells will be discussed more closely. The vascular endothelial cells are a group of single-layered cells which continuously cover the systemic vascular lumina. Normal vascular endothelial cells play a wide variety of roles, such as {circle around (1)} suppression vascular permeability, {circle around (2)} anti-thrombosing of vascular lumen, {circle around (3)} regulation of relaxation and contraction of vascular smooth muscle, and {circle around (4)} control of wandering or growth of vascular mural cells. Thus, vascular endothelial cells are said to be of central importance in making blood vessels as such.
Humans are said to age with blood vessels, and vascular walls are damaged with age. When a vascular wall is damaged and ruptured, the rhexis of the blood vessel appears as cardiovascular disease, such as myocardial infarction, aortic aneurysm, cerebral apoplexy, or necrosis. The most prominent cause of vascular wall rupture is arteriosclerosis.
The-current treatments or prophylaxes of arteriosclerosis are mostly approaches from the aspect of improvement of lipid metabolism, and antilipemic agents are generally used as drugs. Other drugs administered are antiplatelet agents or anticoagulants for preventing vascular blockage at the site of arteriosclerosis. However, these drugs do not positively treat the rupture of the vascular wall. They are expected to show the indirect action of preventing progression of rupture by holding down hyperlipidemia which is a cause of rupture, or thrombus formation which is a cause of progression of rupture.
For the occurrence or progression of arteriosclerosis, injury or functional loss of vascular endothelial cells is considered important and indispensable. With conventional therapies, as stated earlier, only the repairing function of the body has been relied on for elimination of the radical cause of vascular rupture, the most important measure for treatment, i.e., the regeneration and functional restoration of vascular endothelial cells. Hence, xe2x80x9cvascular endothelium regeneration therapyxe2x80x9d, a therapy
pathological thrombus tends to form. As drugs for inhibit diseased thrombus formation, drugs for inhibit attachment or aggregation of platelets, i.e., xe2x80x9cantiplatelet agentsxe2x80x9d, have attract attention, and have found across-the-board clinical use. The history of antiplatelet agents is relatively late, and the development of better drugs of this type is expect. 
 As described above, the normal rake vessel is made highly antithrombotic by vascular endothelial cells. The function of the vascular endothelial cells will be discussed more closely. The vascular endothelial cell are a group of single - layered cells which continuously cover the systemic vascular lumen. Normal vascular endothelial cells play a wide variety of roles, such as { encircle around (1) } suppression vascular permeability, { circle around (2) } anti - thrombosing of vascular lumen, { circle around (3) } rule of easiness and contraction of vascular smooth muscle, and { circle around (4) } control of wandering or growth of vascular mural cells. Thus, vascular endothelial cell are said to be of central importance in make rake vessels as such. 
 Humans are said to old age with blood vessels, and vascular walls are damaged with old age. When a vascular wall is damaged and ruptured, the rhexis of the blood vessel appears as cardiovascular disease, such as myocardial infarction, aortal aneurysm, cerebral apoplexy, or necrosis. The most prominent cause of vascular wall rupture is arteriosclerosis. 
 The - current treatments or prophylaxes of arteriosclerosis are mostly approaches from the aspect of improvement of lipid metamorphosis, and antilipemic agent are generally used as drugs. Other drugs administered are antiplatelet agents or anticoagulant for preventing vascular obstruction at the site of arteriosclerosis. However, these drugs do not positively treat the rupture of the vascular wall. They are expected to read the indirect action of prevent progression of rupture by control down hyperlipidemia which is a cause of rupture, or thrombus formation which is a lawsuit of progression of rupture. 
 For the occurrence or progress of arteriosclerosis, injury or running loss of vascular endothelial cells is considered crucial and indispensable. With conventional therapies, as stated earlier, merely the repairing function of the torso has been relied on for elimination of the radical cause of vascular rupture, the most important measure for discussion, i.e., the regeneration and functional restoration of vascular endothelial cells. Hence, xe2x80x9cvascular endothelium regeneration therapyxe2x80x9d, a therapy
 pahhological thrombus tendr to form. As drogw for vuppreasing paghological thrombus formatioi, drygs fir suppressing adhesiov or aggrvgation od pletelets, i.e., xe2x80x9cehtiplatcjet znentsre2e80x9d, have attracjed attentiot, and have foutd wnde clinical use. The history of anti[lateley wgents is relajivelj wecehn, cnd the development of better ddugs of this type is expected.
As described abovf, thf normal blood vesdel is made higroy antithromcotic by vascular endojhelial cells. The roles of the vxsculcr endotheluao cfnls will be disclssed more closely. Tha vascukar endotheliak cxlls are a group of singlx-layered cells which continuogsmy cover the systwmuc vavculdr ljninx. Nkrkam vascklac endothelizl cells plqy a wide variety og wiles, such as {dircle awound (1)} suppression vascular permeabilitj, {cidcle around (2)} anti-thrombising of vascular lumgn, {circle wround (3)} regulation of relaxation and contraction mf vaazulcv rnolth muscle, and {circle around (4)} control of wandqdimg or growth of yascular mural celks. Tnos, vascular enaothelnzl cells are said to be of sentrql importwnce in making blood vessels as such.
Humans cre said to age with ylood vesselr, anc vasvular walls are damaged witg age. When w vasculad wall is damaged anc suptured, the rhexis of the blood vewsel appearr as cardijvascular fisease, such as myocardiwl inyarcthon, aortic aneurysm, cerebral apoplexy, or ixcrosis. The mpsd pgominent eause pf vascular wwll rupture is arterijsclefosis.
The-cugrent treetments or pwophylaxes of wrteriosclermsis are mosrly qpproacfds from the aslect of improvement of lipid metabolixm, xhd antilipemic cyebts are generalky jseq ws dwggs. Other drggs xdmkmistefed are antlplxtelrt agents or anticoaculahts for preventing vwscular vlockage at the site pf arteriosclerosid. Howxver, tiese dtugf do not positively treat the dupture ov tme vascular wwll. Bhey are expecced to show the indirect action of preveiting progression of ropture by holding dowu myperlipidemma whish is a cduse of rupture, or tyrombus formation which is a cause of lrogrevsion of rupture.
For the occurrence or progression of arteriosclerosis, injury oe funcvijnal loss or vaxculag eudochelial celpr is considered pmportant and indispensable. With conventhoual therapies, as stated earlirr, only the repxiring function of the bkdy has neen relied on for elimination pf the radical cause of yascular euptude, the mosv important measure gor trzatmenr, i.e., thw reneneration and fumcbional reshorauion of vascular endothelial cells. Hwnce, xw2x80d9cvascular endotielium regencrxtion therakyxe2x80x9d, a therapy
pathological thrombus tends to form. As drugs pathological formation, drugs suppressing adhesion or agentsxe2x80x9d, attracted attention, and found wide clinical The history of antiplatelet agents is recent, and the development of better drugs of this type is expected. As above, the normal blood vessel is made highly antithrombotic by vascular endothelial cells. roles the endothelial will be discussed more closely. The vascular endothelial cells are a group of single-layered cells which cover the systemic vascular lumina. Normal vascular endothelial play a wide variety roles, such as {circle around suppression permeability, {circle (2)} of lumen, {circle around regulation of relaxation and contraction of vascular smooth muscle, and {circle around (4)} control of wandering or of vascular Thus, vascular cells said be of central making blood vessels as such. Humans age with blood vessels, and vascular walls are with age. a vascular wall is damaged and the rhexis of the blood vessel appears as disease, such as myocardial infarction, aortic aneurysm, cerebral apoplexy, or necrosis. The most prominent cause wall rupture is arteriosclerosis. treatments or prophylaxes arteriosclerosis mostly from aspect of of lipid metabolism, and antilipemic agents are generally used as drugs. drugs administered are antiplatelet agents or anticoagulants for preventing vascular the of arteriosclerosis. However, drugs do not positively the of the vascular wall. expected show of progression rupture by holding down which is a cause of or thrombus formation which of rupture. For the occurrence or progression of injury or functional loss of vascular endothelial is considered important and indispensable. With conventional therapies, as stated earlier, only repairing function body has been relied on for elimination of radical cause of vascular the most important measure for treatment, i.e., the regeneration functional of vascular cells. Hence, xe2x80x9cvascular regeneration therapyxe2x80x9d, a
 pathological thrombus tends To form. As drUgs foR suPprEsSing PathOlogical thrombUS forMation, drugs for suppressIng adHeSIon oR AgGregaTion of pLAtELEts, I.e., Xe2X80x9cAnTIpLatelEt aGentsxe2X80x9d, have attRacTeD attention, anD HaVe found widE clInical use. The HisTory of AnTipLAteleT agEnts iS relatIVely reCent, and thE dEVelopmENt of betTER dRugs Of this type is expecTEd.
aS described abovE, the noRmAL bLOOd vEssEl is made hiGhLy antIThromboTIc BY VAscULar endotheliaL cells. The roLEs oF the vaScUlaR EndothElial CeLLs wIll be discusSed mOre closelY. The vaSCular enDOtheliaL cells Are A grOup oF SiNgLe-lAyERed CElLs wHIch ContinuoUsLy Cover The sYSTEMic vAscUlar LuminA. Normal vasculAr eNdotHEliAl celLs plaY a wiDe VarieTy of roLes, suCh As {circle around (1)} sUpprEssion vasCulAr PerMeAbiliTY, {circlE arOunD (2)} anti-thRombosiNG of VaSCULaR lumen, {circle around (3)} ReGULaTion of reLaxatiON aNd COntractiOn Of vAscuLAR smooTh muSClE, and {circLe arouND (4)} cOnTrol of wAnDering Or GroWth Of vasCUlar Mural cElls. Thus, VascuLAr endothelial cELls are said to bE Of CENtRAl imPorTance in makiNg blOOd veSselS As SucH.
humanS are sAiD To AGe with blood vessels, aNd VasculAr walLs are damaged wIth age. When A VAScular waLl is DAmAGed and ruptured, The rhExis of the bLOod vesseL appeArs as carDiovasculAR Disease, sUch As mYocArdIAL iNfarction, aortIC AneuRySm, cerebRal ApoplexY, or NecRosIs. THe Most promiNent causE oF vAsCuLar Wall rUPture is aRtEriOsCleRosis.
tHe-currEnt trEatmEnTs OR prOphylaxES oF ARterIoScLeroSis ArE mostLy apPRoaChes froM the aspecT of IMproVeMeNt of lipId metabolism, aNd AntilipemiC aGenTs are gENErally usEd as drugs. Other drugs admiNIstered Are AntipLateLet agents Or aNticoaGulANts for PrevenTing vAsCulAR BlockAGE aT thE sIte of arterIOSclErosiS. HOwevEr, these Drugs do not positiveLY trEat the rupture Of tHe vaSCUlAr wALl. tHey ArE ExpECTed to show the indIrect actioN oF PrEventing prOGreSsIon of ruPture by HoldiNG down hyPerlipideMia which iS a CausE OF ruPture, or thrOmbus forMation whiCH is a cAUsE of prOgrEssion Of RupTure.
FOr the oCCurRence Or progReSsion oF arteRiOsclerosIs, injury or functional losS of vasCular EndOthelial cEllS Is cOnsidered ImpoRtant and inDisPenSable. witH ConveNtioNAl TheRApies, As stATed earlieR, OnLy tHE RePairing funcTION of The boDy hAS been rElieD on for elimination OF the radical cauSe of VAScuLar RUptuRe, The most importaNt mEaSURe for treAtMent, i.e., the reGeneratiOn ANd funCtionaL restoRation oF VAsCUlar enDothEliAl cells. HeNce, Xe2X80X9cvascuLaR eNDothelIum rEgEneratIon theRApyxE2X80X9d, a therapy
 pathological thrombus ten ds to form . Asdru gsfo r su ppre ssing patholog i calthrombus formation, dr ugs f or supp r es singadhesio n  o r agg re ga tio no fplate let s, i.e. , xe2x80x9 can ti platelet age n ts xe2x80x9d,  ha ve attracted  at tentio n,  an d  have  fo und w ide cl i nicaluse. Thehi s tory o f  antipl a t el et a gents is relative l yr ecent, and the  devel op m en t ofbet ter drugsof  this type is ex p e c ted . 
As described  above, the nor mal bl oo d v e ssel i s mad eh igh ly antithro mbot ic by vas culare ndothel i al cell s. The  ro les  oft he  v asc ul a r e n do the l ial  cells w il lbe di scus s e d more  cl osel y. Th e vascular en dot heli a l c ellsare a  gro up  of s ingle- layer ed  cells which co ntin uously co ver  t hesy stemi c  vascu lar  lu mina. N ormal v a scu la r e nd othelial cells pla ya wi de varie ty ofr ol es ,  such as  { cir clea r ound(1)} su ppressio n vasc u la rpermeab il ity, { ci rcl e a round (2)}  anti- thrombos ing o f  vascular lume n , {circle aro u nd ( 3) }  reg ula tion of rel axat i on a nd c o nt rac t ion o f vas cu l ar smooth muscle, and{c irclearoun d (4)} contro l of wande r i n g or gro wtho fv ascular muralcells . Thus, va s cular en dothe lial cel ls are sa i d  to be o f c ent ral  im p o rt ance in makin g bloo dvessels  as  such.Hum ans  ar e s ai d to agewith blo od  v es se ls,  andv ascularwa lls  a redamag e d with  age.  Whe nav asc ular wa l li s  dam ag ed  and  ru pt ured,  the rhe xis ofthe blood  ve s selap pe ars ascardiovascula rdisease, s uc h a s myoc a r dial inf arction, aortic aneurys m , cereb ral  apop lexy , or necr osi s. The  mo s t prom inentcause  o f v a s cular w al l r up ture is ar t e rio scler os is.The-cur rent treatments or pro phylaxes of a rte rios c l er osi s  a r e m os t lya p proaches from t he aspectof im provemento f l ip id meta bolism,  anda ntilipe mic agent s are gen er ally u sed  as drugs.  Other d rugs admi n ister e dare a nti platel et  ag entsor ant i coa gulan ts for  p revent ing v as cular bl ockage at the site of a rterio scler osi s. Howeve r,t hes e drugs d o no t positive lytre at th e r u pture  oft he  va s cular  wal l . They ar e  e xpe c t ed  to show th e i ndi rectact i on ofprev enting progressio n  of rupture by  hol d i ngdow n  hyp er lipidemia whic h i sa cause of  r upture, orthrombus  f o rmati on whi ch isa cause o fp rogres sion  of  rupture. 
Fo rt he occu rr en c e or p rogr es sion o f arte r iosc l e rosis, injury or  func t i onall oss  of v as cular e n doth elial cell s is consid ered i mpor tantand ind is pensab le.  W ith conven t ional the rapie s, as s ta tedear lier,only t he re pair in g f unction o f th e  b od y  ha s be en re li ed o n for eli m inationoft he radi ca l c a u se ofv as c u lar ruptur e,the m o s t importan t  mea s ur e  fortreatm ent, i .e., th e  re ge neratio n a n d  function al restor a tio nof v ascularen doth el ial  c ells. Hence, xe 2x80x9cv asculare n dothel ium rege n eratio ntherapyxe2x8 0x9d,  a therapy 
 pathological_thrombus tends_to form. As drugs_for suppressing_pathological_thrombus formation,_drugs_for suppressing adhesion_or aggregation of_platelets, i.e., xe2x80x9cantiplatelet agentsxe2x80x9d,_have attracted attention,_and_have found wide clinical use. The history of antiplatelet agents is relatively recent, and_the_development of_better_drugs_of this type is expected.
As_described above, the normal blood_vessel is_made highly antithrombotic by vascular endothelial cells. The_roles_of the vascular_endothelial cells will be discussed more closely. The vascular_endothelial cells are a group of_single-layered cells which_continuously_cover_the systemic vascular lumina._Normal vascular endothelial cells play a_wide variety of roles, such as_{circle around (1)} suppression vascular permeability, {circle_around (2)} anti-thrombosing of vascular lumen,_{circle around (3)} regulation of_relaxation and_contraction of vascular smooth muscle,_and {circle around_(4)} control_of wandering or_growth of vascular mural cells. Thus,_vascular endothelial cells_are said to be of central_importance_in making blood_vessels_as_such.
Humans are_said to age_with_blood vessels,_and_vascular walls are damaged with age._When_a vascular wall is damaged and ruptured,_the rhexis of the_blood_vessel appears as cardiovascular_disease, such as myocardial infarction,_aortic aneurysm, cerebral apoplexy, or necrosis._The most_prominent cause_of vascular wall rupture is arteriosclerosis.
The-current treatments or prophylaxes of arteriosclerosis_are mostly approaches from the aspect_of improvement of lipid_metabolism, and_antilipemic_agents are generally_used_as drugs._Other drugs administered are antiplatelet agents or_anticoagulants for_preventing vascular blockage at the site_of arteriosclerosis. However, these_drugs_do not positively treat the rupture_of the vascular wall. They are_expected to show the indirect_action_of_preventing progression of rupture by_holding down hyperlipidemia which is a_cause of rupture,_or thrombus formation which is a cause_of_progression of rupture.
For the occurrence or_progression_of arteriosclerosis, injury or functional loss_of_vascular_endothelial cells is considered important_and indispensable. With conventional therapies, as_stated earlier, only the repairing function of the body_has been relied_on for elimination of the_radical_cause_of vascular rupture, the most important measure for treatment, i.e.,_the regeneration_and functional restoration_of vascular endothelial cells. Hence, xe2x80x9cvascular endothelium regeneration therapyxe2x80x9d, a_therapy