Add ess o co espondence: A i Mennande , MD, Hea Cen e , Ca diac Resea ch, Tampe e Uni e si y Hospi al and
Tampe e Uni e si y Medical School; Ensi ie 4; 33520 2000 Tampe e-Finland
Phone: +358 3 31164945 E-mail: [email p o ec ed]
Accep ed Da e: 03.09.2018 A ailable Online Da e: 26.10.2018
©Copy igh 2018 by Tu kish Socie y o Ca diology - A ailable online a www.ana oljca diol.com
DOI:10.14744/Ana olJCa diol.2018.42223
O iginal In es iga ion 289
Ee u Niinimäki, Ville Pynnönen, I ana Kholo a, Timo Paa onen, A i Mennande *
Depa men s o Pa hology, Fimlab Labo a o ies, *Hea Cen e , Ca diac Resea ch, Tampe e Uni e si y Hospi al and
Tampe e Uni e si y Medical School; Tampe e-
Finland
Neo ascula iza ion wi h ch onic in lamma ion cha ac e izes
ascending ao ic dissec ion
In oduc ion
The main goal o su ge y o he dila ed ascending ao a is
o p e en ao ic dissec ion (AD) and up u e (1, 2). AD consis s
o an ao ic wall ea in a angen ial ashion and ep esen s he
ul ima e up u e due o ao ic wall weakness. Pa hophysiologi-
cally, AD and ao ic up u e a e in e ela ed and a e mani es ed
by he ana omical si e o he ao ic ea (2). Despi e he sudden
occu ence o he ao ic ea , he ascending ao a may ha e
unde gone a ch onic emodeling phase o issue weakening, in-
cluding ao ic wall hypoxia, hype ension, and ch onic in lamma-
ion. Al hough a bo de line o a 5.5 cm diame e o he ascending
ao a is ega ded as he h eshold in enhancing he isk o AD
(2), he e is inc easing e idence ha ao as wi h an e en smalle
diame e may lead o AD (3). The decision o he ex ension o e-
sec ion o he ao a du ing su ge y is challenging, as one would
aim a p e en ing AD a e su ge y.
The pe iope a i e e alua ion o he esec ed ao ic wall du -
ing su ge y o ascending ao a may e eal suscep ibili y o AD
necessi a ing u he ex ension o su ge y. Mos AD occu s in
he ou e hi d o he media close o he ad en i ia (4). This si e is
cha ac e ized by asa aso um ha pa icipa es in he nu i ion
o he ao ic wall (4). The signi icance o endo helial ac i a ion
o asa aso um in ao ic pa hogenesis is unde discussion (5).
A e ial neo ascula iza ion may be egula ed by ch onic in lam-
ma ion, sugges ing ha hypoxia alone is no leading o issue e-
modeling (6). Recen expe imen al s udies sugges ha he egu-
la ion o angiogenesis is dependen on endo helial ac i a ion (7).
We s udied he ascula eac i i y o he ao ic wall by cha -
ac e izing he angiogenic his ology o he ascending ao a as
exp essed by CD31. We hypo hesized ha ch onic in lamma o y
Objec i e: Neo ascula iza ion o he ao ic wall may be associa ed wi h ao ic dissec ion (AD). Ao ic wall endo helial CD31 deposi ion oge he
wi h ch onic in lamma ion indica es angiogenesis ha may lead o issue dis up ion. We s udied he p esence o neo ascula iza ion o he as-
cending ao ic wall by cha ac e izing CD31 posi i e endo helial cells.
Me hods: Ao ic wall ou ine his ology and immunohis ochemis y o CD31, T- and B-lymphocy es, plasma cells, mac ophages, endo helial cells,
smoo h muscle cells, and cell p oli e a ion we e pe o med on 35 selec ed pa ien s who unde wen su ge y o he ascending ao a, and he
samples we e g ouped acco ding o he p esence o AD.
Resul s: Th ee subjec s wi h Ma an synd ome we e excluded om he s udy. A o al o 14 ou o 32 pa ien s had AD. A o al o 18 pa ien s
we e ope a ed on due o dila a ion only. Ch onic in lamma ion o he ad en i ia (p=0.003), media (p=0.001), and in ima (p=0.005) was inc eased
in AD. Neo ascula iza ion was p edominan in he ou e hi d medial laye in AD (p=0.037), co esponding o he si e o ao ic wall dis up ion. A
ecei e ope a ing cha ac e is ic cu e analysis showed ha neo ascula iza ion was associa ed wi h AD (AUC 0.750; SE 0.092; p=0.022; 95% CI
0.570–0.930).
Conclusion: Endo helial immunohis ochemis y con i ms neo ascula iza ion o he ou e hi d medial laye du ing AD. Ao ic wall emodeling
including neo ascula iza ion cha ac e izes AD. Ch onic in lamma ion and neo ascula iza ion o he dila ed ascending ao a sugges suscep ibil-
i y o AD. (Ana ol J Ca diol 2018; 20: 289-95)
Keywo ds: neo ascula iza ion, ascending ao ic dissec ion, ch onic in lamma ion, CD31
ABSTRACT
Niinimäki e al.
Ao ic dissec ion and neo ascula iza ion
Ana ol J Ca diol 2018; 20: 289-95
DOI:10.14744/Ana olJCa diol.2018.42223
290
emodeling o he ascending ao a is associa ed wi h dila a ion
o he ao ic wall, and neo ascula iza ion o he ascending ao -
ic media may de e mine he a e o he dila ed ao ic wall. Us-
ing an ex ensi e immunohis ochemical analysis and de ec ion o
CD31-posi i e endo helial cells o he medial laye , we e alua ed
whe he neo ascula iza ion is associa ed wi h AD.
Me hods
S udy p o ocol and su ge y
A e an ins i u ional e iew boa d app o al, he need o in-
o med consen was wai ed. The ascending ao ic wall esec ion
o 35 consecu i e pa ien s unde going su ge y o ascending ao -
a was ob ained and p ocessed o his ology. An ascending ao -
ic aneu ysm was p eope a i ely con i med and e alua ed wi h
compu ed omog aphy (CT). Acco ding o ou ins i u ional policy,
ao ic aneu ysm included an ao ic diame e wide han 5.5 cm o
ao ic g ow h g ea e han 1 cm in a yea . This de ini ion was ad-
jus ed o he p esence o Ma an synd ome, gende , pa ien size,
and symp oms, including AD acco ding o he Yale Cen e c i e ia
(2). Su ge y was pe o med be ween Decembe 2009 and Augus
2014, and cases o ascending ao as including AD p ocessed o
his ology we e en olled. Th ee pa ien s wi h Ma an synd ome
we e excluded. The e we e 14 pa ien s wi h acu e AD including
onse o symp oms ha las ed less han 7 days.
The decision on he ex ension o esec ion and su gical ech-
nique was a he disc e ion o he ope a ing su geon. When an
ao ic aneu ysm including he sino ubula junc ion (STJ) was
es ima ed as he eason o ao ic egu gi a ion, STJ was ai-
lo ed o a sui able g a in a sup aco ona y ashion. Whene e
dila a ion included he ao a oo , a adical esec ion o he di-
la ed ascending ao a oge he wi h he oo and he ao ic al e
was pe o med. The g a size was es ima ed by he p incipal
su geon. The en y ea s we e loca ed in he middle po ion o
he ascending ao a acco ding o p e-ope a i e CT and in a-
ope a i e assessmen . Since he su gical p ocedu e was pe -
o med upon su gical decision, he sample was p ocu ed om
he middle o he esec ed diseased a ea o he ascending ao a
a he icini y o STJ.
His ology and immunohis ochemis y
Two o i e blocks o esec ed ascending ao a we e embed-
ded in pa a in, cu o 4-mm- hick segmen s and s ained wi h
hema oxylin and eosin, Ve hoe - an Gieson, Elas ase- an Gie-
son, and Pe iodic Acid-Schi . A ep esen a i e 1-cm-long piece
o ascending ao ic wall co esponding o all di e en s aining
was e alua ed sys ema ically o all esec ed samples p ocu ed
du ing su ge y.
Ao ic wall his ology and immunohis ochemis y we e pe -
o med using Ven ana Li esciences Benchma k XT S aining
module o leukocy es, T- and B-lymphocy es, plasma cells,
mac ophages, smoo h muscle cells, cell p oli e a ion, elas ase,
and an Gieson s aining. The samples we e u he in es iga ed
o p esence and locali y o neo ascula i y wi hin he ao ic
wall; capilla ies wi h endo helial cells we e e alua ed using a
polyclonal abbi an ibody o CD31 (dilu ion 1:2500) (DakoCyma-
ion). Ven ana Li esciences An ibody Dilu ion Bu e was u ilized
o dilu ion media. The heigh s o di e en laye s (ad en i ia, me-
dia, and in ima) we e calcula ed o each sample. In lamma o y
cells, he in ensi y o in lamma ion, cell p oli e a ion, medial de-
gene a ion, in ima cellula i y, and hickness we e es ima ed as
p e iously desc ibed and exp essed as poin sco e uni s (PSU)
in he h ee ao ic wall laye s acco dingly (8). B ie ly, in lamma-
ion was g aded as none, mild, mode a e, o se e e (0, 1, 2, o 3).
Medial degene a ion was g aded as pa chy, mode a e, o se e e
again on a scale o 0–3. In ima cellula i y and hickness we e
es ima ed acco ding o an a bi a y scale om 0–3, whe e 0 indi-
ca ed no mal in ima wi h a single endo helial cell laye ; 1, in ima
cellula i y and hickness less han 25% as compa ed wi h he
media; 2, in ima cellula i y and hickness mo e han 25% bu less
han 50% as compa ed wi h he media; 3, in ensi e in ima cellu-
la i y and hickness mo e han 50% as compa ed wi h he media.
Quan i ica ion o medial neo ascula iza ion
Pla ele endo helial cell adhesion molecule 1 (PECAM-1),
also known as CD31 (clus e o di e en ia ion 31), is exp essed
a
b
Figu e 1. Rep esen a i e immunohis ochemis y (x20) o CD31 o he
ascending ao a. No e he CD31 posi i i y (whi e a ow) in he ou e
hi d medial laye o he ascending ao a sugges ing suscep ibili y o
ao ic dissec ion in (a) The onse o dissec ion (whi e b acke s) in b a
he si e o CD31 posi i i y (whi e a ow). Inle s (x40) a he bo om le
co ne show he si e o in e es s in de ail.
Niinimäki e al.
Ao ic dissec ion and neo ascula iza ion
Ana ol J Ca diol 2018; 20: 289-95
DOI:10.14744/Ana olJCa diol.2018.42223 291
in high amoun s in endo helial cell junc ions (9). As CD31 may
be exp essed by leukocy es and pla ele s (10), angiogenesis
was de ined by accoun ing CD31-posi i i y, including only cap-
illa y-like mo phology wi h a con inuous unin e up ed endo he-
lial monolaye wi hin he media laye . Fo local quan i ica ion o
CD31-posi i i y, we ca ego ized he media in o h ee equal pa s;
he inne media consis ing o he inne mos media adjacen o
he in ima, he ou e media adjacen o he ad en i ia, and he
middle media be ween hese wo media laye s, espec i ely. The
o al numbe o posi i ely s ained CD31 new essels was coun -
ed pe squa e millime e in ou a bi a ily selec ed a eas, which
showed he mos inc eased densi y o capilla y-like mo phology
(ho spo s).
Follow-up p o ocol
Documen a ion o mo ali y and mo bidi y was a ailable
o all he pa ien s. Fo he included s udy pa ien s, ollow-up
consis ed o physical examina ion and echoca diog aphy a 3
mon hs a e su ge y, and on-demand he ea e including CT.
S a is ical analysis
CD31-posi i e s aining was p edominan ly ound in he me-
dia, a he bo de o he ad en i ia including o ma ion o small
essels (Fig. 1). To seek clinical ele ance associa ed wi h im-
munohis ochemis y, he pa ien s we e di ided in o wo g oups
in acco dance wi h he his ologically con i med p esence o AD.
Al hough his opa hology con i ms AD, indices o in lamma ion,
hemo hage, o ib osis do no acili a e he empo al diagnosis
o AD (11). The pa ien s we e ca ego ized in keeping wi h he
p esence o dissec ion (AD+) and dila a ion only (AD-). All s udy
pa ien s we e ollowed o a pe iod o 3 mon hs. Quan i a i e
a iables a e lis ed as he mean and s anda d e o o he mean.
Ca ego ical a iables a e s a ed as coun and pe cen age. S a-
is ical analysis was pe o med wi h he SPSS e sion 22.0. The
Mann-Whi ney U es was used o con inuous a iables, and
he chi-squa ed es o ca ego ical analysis. The associa ion o
CD31 wi h AD was assessed by he ecei e ope a ing cha ac-
e is ic cu e (ROC) analysis. P- alues less han 0.05 we e con-
side ed s a is ically ele an .
Resul s
Demog aphics
Eigh een pa ien s had ascending AD, while 14 ou o 32 pa-
ien s we e ope a ed o acu e AD (Table 1). The mean age was
Table 1. Pa ien demog aphics
All pa ien s AD+ AD– P- alue
Numbe o pa ien s 32 14 18
Age (yea s) 64±2 69±2 59±3 0.010
Male, n 22 (69%) 8 (57%) 14 (78%) 0.267
Hype ension, n 13 (41%) 6 (43%) 7 (39%) 1
Diabe es, n 1 (3%) 1 (7%) 0 0.438
Hype choles e olemia, n 3 (9%) 0 3 (17%) 0.238
Vasculi is, n 1 (3%) 0 1 (6%) 1
A h i is, n 3 (9%) 3 (22%) 0 0.073
As hma, n 2 (6%) 1 (7%) 1 (6%) 1
Myoca dial co ona y a e y disease, in a c ion, n 7 (22%) 3 (22%) 4 (22%) 1
P e ious ca dio ho acic ope a ion
Co ona y a e y bypass su ge y, n 2 (6%) 2 (15%) 0 0.183
Co ec ion o ao ic coa c a ion, n 1 (3%) 0 1 (6%) 1
Co ec ion o abdominal ao a aneu ysm 1 (3%) 1 (7%) 0 0.438
Mid-ascending ao a diame e , mm 58±2 59±3 57±3 0.323
2-cusp ao ic al e, n (%) 8 (25%) 1 (7%) 7 (39%) 0.053
Ao ic al e insu iciency
Mode a e o se e e, n 12 (38%) 4 (29%) 8 (45%) 0.471
Ao ic al e s enosis
Mode a e o se e e, n 12 (38%) 1 (7%) 11* (61%) 0.003
*includes i e pa ien s wi h combined ao ic al e disease, P=0.001
AD - ao ic dissec ion
Niinimäki e al.
Ao ic dissec ion and neo ascula iza ion
Ana ol J Ca diol 2018; 20: 289-95
DOI:10.14744/Ana olJCa diol.2018.42223
292
64±2 yea s. Hype ension and co ona y a e y disease we e
equally dis ibu ed among bo h g oups. One pa ien wi hou AD
had unspeci ied asculi is o he ao ic wall. Fou pa ien s wi h
AD and eigh wi hou AD had ao ic al e insu iciency. Ele en
ou o 18 pa ien s wi hou AD had ao ic al e s enosis, includ-
ing i e pa ien s wi h combined ao ic al e disease, in con as
o only one ao ic al e s enosis in a pa ien wi h AD. The mean
ao ic diame e was 58±2 mm o all pa ien s.
Ope a i e echnique
In pa ien s wi h AD, su ge y included ei he a Ben all- ype
ope a ion wi h an ao ic al e p os hesis, o eplacemen o
he ascending ao a only (Table 2). In eigh pa ien s wi hou
AD, he ao ic oo was no ope a ed on. A mechanical o
biologic al e was eplaced oge he wi h a p os hesis en-
compassing he ascending ao a dis ally om he sino ubula
junc ion in i e pa ien s wi hou AD. In h ee pa ien s wi hou
AD and wi hou ao ic al e disease, only he ascending ao a
was eplaced.
Pe iope a i e indings, his ology, and immunohis ochemis y
His ology e ealed h ee cases o ao i is, o which wo had
AD+ (Tables 3 and 4). The in ensi y o ch onic ad en i ial, me-
dial, and in imal in lamma ion was inc eased in AD+ as com-
pa ed wi h AD− (2.2±0.3 s. 1.3±0.2, p=0.03, 1.4±0.3 s. 0.3±0.1,
p<0.001, and 1.6±0.3 s. 0.7±0.2, p=0.005, espec i ely). The me-
dia showed inc eased cell p oli e a ion in AD+ as compa ed
wi h AD− (1.5±0.3 s. 0.4±0.2, p=0.002). An inc eased numbe
o mac ophages and T-cells o he in ima we e ound in AD+
as compa ed o AD− (1.9±0.2 s. 1.2±0.2 p=0.032 and 1.4±0.2
s. 0.6±0.2, p=0.006, espec i ely). The ou e hi d laye o he
media a he icini y o he ad en i ia exp essed an inc eased
numbe o cy oplasmic CD31-posi i i y in AD+ as compa ed
wi h AD− (5.1±1.1 s. 2.4±0.7, p=0.037), and co esponded o
he si e o AD ea (Fig. 1).
Table 2. Ope a i e de ails acco ding o su gical e alua ion o ex ension o diseased ao a
All Pa ien s AD+ AD– P- alue
32 14 18
G a eplacemen o oo and ascending ao a
Mechanical condui 9 (28%) 3 (22%) 6 (33%) 0.694
Biological condui 8 (25%) 4 (29%) 4 (22%) 0.703
G a eplacemen o ascending ao a
Mechanical al e+p os hesis 2 (7%) 0 2 (11%) 0.492
Biological al e+p os hesis 3 (10%) 0 3* (17%) 0.238
P os hesis 10 (32%) 7 (50%) 3 (17%) 0.062
Addi ional p ocedu e
Co ona y a e y bypass su ge y 4 (13%) 2 (15%) 2 (11%) 1
*includes ao oplas y
AD - ao ic dissec ion
Table 3. His ology and quan i a i e immunohis ochemis y
Mean g ade o s aining
mm mm All Pa ien s AD+ AD– P- alue
Ad en i ia
T-cells 1.4±0.2 1.8±0.3 1.1±0.2 0.077
B-cells 1.0±0.2 1.2±0.4 1.0±0.2 0.791
Mac ophages 1.8±0.2 2.2±0.2 1.5±0.2 0.068
Plasma cells 0.6±0.2 0.9±0.3 0.6±0.2 0.201
In lamma ion 1.6±0.2 2.2±0.3 1.3±0.2 0.003
P oli e a ion 1.5±0.2 1.6±0.2 1.3±0.4 0.561
Media
T-cells 0.6±0.2 0.8±0.3 0.5±0.2 0.476
B-cells 0.2±0.1 0.3±0.2 0.1±0.6 0.175
Mac ophages 1.2±0.2 1.5±0.3 1.0±0.3 0.207
Plasma cells 0.4±0.2 0.3±0.2 0.5±0.4 0.424
In lamma ion 0.8 ± 0.2 1.4±0.3 0.3±0.1 0.001
P oli e a ion 0.9±0.2 1.5±0.3 0.4±0.2 0.002
Degene a ion 1.5±0.2 1.7±0.3 1.4±0.3 0.466
Elas ase 1.6±0.2 1.6±0.2 1.6±0.3 0.968
In ima
T-cells 1.0±0.2 1.4±0.2 0.6±0.2 0.006
B-cells 0.1±0.1 0.3±0.2 0 0.072
Mac ophages 1.5±0.2 1.9±0.2 1.2±0.2 0.032
Plasma cells 0.7±0.2 0.7±0.2 0.5±0.4 0.622
In lamma ion 1.1±0.2 1.6±0.3 0.7±0.2 0.005
P oli e a ion 0.9±0.2 1.0±0.2 0.5±0.4 0.206
Thickness 2.0±0.3 1.9±0.3 2.1±0.4 0.706
Cellula i y 1.6±0.2 1.7±0.2 1.3±0.2 0.328
Mean g ade o s aining exp essed as poin sco e uni s/mm2
AD - ao ic dissec ion
Niinimäki e al.
Ao ic dissec ion and neo ascula iza ion
Ana ol J Ca diol 2018; 20: 289-95
DOI:10.14744/Ana olJCa diol.2018.42223 293
ROC analysis and ou come
A ROC analysis showed ha he local endo helial ac i -
i y was associa ed wi h AD (AUC 0.750; SE 0.092; p=0.022; 95%
CI 0.570–0.930, Fig. 2). Two pa ien s wi h AD died sho ly a e
su ge y: a 55-yea old p eope a i ely unconscious pa ien and
an 88-yea old ha expe ienced AD up u e be o e he onse
o hypo he mia. Two pa ien s wi hou AD died wi hin 1 week o
su ge y, due o ce eb al in a c ion caused by hypo ension and
ce eb al emboli a su ge y.
Discussion
Based on his s udy, local neo ascula iza ion o he ou e
medial laye indica es ac i e emodeling o he ao ic wall as-
socia ed wi h AD; his ological cha ac e is ics o he ascending
ao ic wall may be in es iga ed o e eal endo helial ac i a ion
o newly o med capilla ies o he media laye acco ding o he
CD31 posi i i y. Toge he wi h neo ascula iza ion, an inc eased
numbe o p oli e a i e cells and mac ophages is s ongly sug-
ges i e o ch onic in lamma ion in pa ien s wi h AD.
Dila a ion o he ascending ao a alone does no undeniably
lead o AD. Hype ension and a amily his o y o dila a ion o
he ao a may inc ease he isk o dila a ion pe se, bu AD
seems o occu in some ins ances quasi-unexpec edly, while
he ao ic diame e has no eached he h eshold alue o 5.5
cm2. Acco ding o a la ge e e al cen e , AD was missed up o
38% o cases on ini ial e alua ion and i s es ablished in 28%
o pa ien s only a pos mo em examina ion (12). While adi-
ional CT and echoca diog aphy may no p o ide an accu a e
es ima ion o he isk o AD, molecula imaging has eme ged
as a plausible and p omising op ion (13). Risk s a i ica ion o
AD may bene i om unde s anding he he e ogeneous pa ho-
genesis o he in lamma o y p ocess and angiogenesis du ing
ao ic emodeling. Imaging modali ies, such as posi on emis-
sion omog aphy, single pho on emission CT, and magne ic
esonance imaging, wi h he aid o acing ch onic in lamma-
ion and neo ascula iza ion, a e in ensi ely s udied o clinical
ansla ion (13).
The clinician c a es o an applicable means o diagnose ac-
cu a ely an ao a p one o AD. This s udy emphasizes he impo -
ance o in es iga ing bo h ch onic in lamma ion and neo ascu-
la iza ion ha oge he may o m a igge o AD. This message
impo an ly adds o he clinical ansi ion o imaging modali ies
ha a e based on acing ch onic in lamma ion and neo ascu-
la iza ion (13). An ao ic si e cha ac e ized by mic o essel o -
ma ion and in lamma ion du ing p og ession o ascending ao ic
dila a ion (14) enhances awa eness o he need o ea ly su gi-
cal in e en ion o p e en AD.
The onse o AD includes e ical up u e o he ao ic wall
o en a he junc ion o he media and ad en i ia (15). This
ao ic wall si e sugges s ha he hypoxic en i onmen o he
media laye may a ac ch onic in lamma o y componen s
and e en ually lead o angiogenesis and issue ea . Endo he-
lial cells o m he inne lining o newly o med capilla ies and
ende he media–ad en i ia bo de suscep ible o he onse o
AD. In lamma ion alone wi hou angiogenesis may no su ice
o ini ia e AD. The e a e spa se da a on he impac o CD31 im-
munohis ochemis y on AD. Dys unc ion o he mic oci cula ion
in he ou e media laye o he ao a may sugges ischemia and
malnu i ion o he ao ic wall, hus inc easing he isk o AD
(4). The impac o ischemia along wi h in imal hype plasia and
hype ension is no demons a ed in ou s udy among he pa-
ien s. I is impo an o dis inguish CD31-s ained endo helial
cells om mac ophages, since p oin lamma o y mac ophages
ha e expe imen ally been shown o in luence he ao ic wall
du ing AD (16).
Neo ascula iza ion is a key ac o o he pa hophysiology o
a ious a e ial diseases, such as a he oscle osis (17), asculi-
is (6), in ac anial a e y aneu ysm (18), and abdominal ao ic
aneu ysm (5). Neo ascula iza ion ba ely seems o be a conse-
Table 4. Quan i a i e immunohis ochemis y o CD31
acco ding o loca ion o s aining
Mean g ade o s aining All pa ien s AD+ AD– P- alue
Media
Ou e laye 3.5±0.7 5.1±1.1 2.4±0.7 0.037
Middle laye 1.7±0.3 2.1±0.6 1.4±0.4 0.258
Inne laye 0.9±0.2 0.7±0.3 1.1±0.4 0.714
Mean g ade o s aining exp essed as poin sco e uni s/mm2
AD - ao ic dissec ion
Figu e 2. Recei e ope a ing cha ac e is ic cu e analysis shows ha
local neo ascula iza ion o he ao ic wall is associa ed wi h AD (AUC
0.750; SE 0.092; P=0.022; 95% CI 0.570–0.930)
1.0
1.0
0.8
0.8
0.6
0.6
1-Speci ici y
Sensi i i y
0.4
0.4
0.2
0.2
0.0
0.0

Niinimäki e al.
Ao ic dissec ion and neo ascula iza ion
Ana ol J Ca diol 2018; 20: 289-95
DOI:10.14744/Ana olJCa diol.2018.42223
294
quence o hypoxia alone, bu i in ol es mechanisms in oduced
by immunology and subsequen ch onic in lamma ion (5, 6, 19).
Acco ding o a p e ious expe imen al model (20), dec eased
ci cula ion o asa aso um, which o en occu s in a e ial hy-
pe ension (17), may inc ease he s i ness o he ou e media
o he ao a, bu an immunological ac i a ion o he ao ic wall
seems p e equisi e o ini ia e an ac i e ea , which leads o AD
(17, 19, 21, 22). Ch onic in lamma ion o all ao ic laye s was
p esen in ou s udy, oge he wi h neo ascula iza ion and AD.
Compa ably, acu e plaque up u e o he a he oscle o ic co o-
na y a e y (23) o he o ma ion o mic ohemo hages wi hin
in ac anial a e y aneu ysms (18) may ep esen disease en i-
ies ini ia ed by he ac i a ion o neo essels (19). I is emp ing
o sugges ha CD31 immunohis ochemis y may e eal a weak
ao ic wall si e p one o AD.
S udy limi a ions
This is a s udy in es iga ing he associa ion o inc eased ao -
ic neo ascula iza ion in a ai ly low numbe o pa ien s wi h o
wi hou AD. Un o una ely, he a e o expansion o he non- e-
pai ed segmen s o he ao a was no e alua ed o co ela e wi h
immunohis ochemis y, pa ly due o he small numbe o pa ien s.
As a pa adigm o compa able issue p epa a ion in his s udy, we
did no sys ema ically in es iga e ao as ob ained om au opsied
cases. Only less han a hi d o he pa ien s had bicuspid ao ic
al e disease, and i is beyond ou scope o discuss he plausible
in e ac ion o speci ic he e ogenic ao ic al e diseases in he
de elopmen o AD. Inc eased ch onic ao ic wall in lamma ion
was associa ed wi h AD oge he wi h neo ascula iza ion, bu
speci ic immunological pa ame e s such as complemen ac i a-
ion emain o be elucida ed.
Conclusion
He e ogenei y o he p og ession o ao ic dila a ion o AD is
expec ed (14). In e ac ing wi h ch onic in lamma ion and associ-
a ed neo ascula iza ion may impac agains he de elopmen o
AD. Taken oge he , we sugges ha CD31 immunohis ochemis y
adds o he unde s anding o he emodeling cha ac e is ics o
he ascending ao a, al hough u he s udies a e clea ly ecom-
mended.
Con lic o in e es : None decla ed.
Pee - e iew: Ex e nally pee - e iewed.
Au ho ship con ibu ions: Concep – I.K., T.P., A.M.; Design – E.N.,
V.P., T.P., A.M.; Supe ision – E.N., T.P., A.M.; Fundings – I.K., T.P., A.M.;
Ma e ials – E.N., V.P., I.K., A.M.; Da a collec ion &/o p ocessing – E.N.,
V.P., A.M.; Analysis &/o in e p e a ion – E.N., I.K., T.P., A.M.; Li e a u e
sea ch – E.N., V.P., A.M.; W i ing – I.K., T.P., A.M.; C i ical e iew – E.N.,
V.P., I.K., T.P., A.M.
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