Introduction: Carbamylation is a nonenzymatic post-translational modification of proteins characterized by the binding of isocyanic acid to amino groups of proteins, which leads to the alteration of their properties. An increase in serum carbamylation-derived products, including homocitrulline (HCit), has been shown to be associated with the development of cardiovascular diseases. Methods: HCit was quantified by LC-MS/MS within extracts of aneurysmal and control human aortas. A mouse model of aortic aneurysm (ApoE−/− mice perfused with angiotensin II and fed with sodium cyanate) was used to evaluate the role of carbamylation in aneurysm development. Results: HCit quantification showed a greater heterogeneity of values in aneurysmal aortas in comparison with control ones. At the maximum diameter of dilation, HCit values were significantly higher (+94%, p < 0.05) compared with less dilated areas. No differences were observed according to aneurysm size or when comparing ruptured and unruptured aneurysms. No significant effect of carbamylation on aneurysm development was observed using the animal model. Conclusions: These results evidenced the accumulation of HCit within aneurysmal aortas but do not allow concluding about the exact participation of protein carbamylation in the development of human abdominal aortic aneurysms.

1.
Anagnostakos
J
,
Lal
BK
.
Abdominal aortic aneurysms
.
Prog Cardiovasc Dis
.
2021
;
65
:
34
43
.
2.
Jaisson
S
,
Pietrement
C
,
Gillery
P
.
Carbamylation-derived products: bioactive compounds and potential biomarkers in chronic renal failure and atherosclerosis
.
Clin Chem
.
2011
;
57
(
11
):
1499
505
.
3.
Jaisson
S
,
Pietrement
C
,
Gillery
P
.
Protein carbamylation: chemistry, pathophysiological involvement, and biomarkers
.
Adv Clin Chem
.
2018
;
84
:
1
38
.
4.
Wang
Z
,
Nicholls
SJ
,
Rodriguez
ER
,
Kummu
O
,
Horkko
S
,
Barnard
J
et al
.
Protein carbamylation links inflammation, smoking, uremia and atherogenesis
.
Nat Med
.
2007
;
13
(
10
):
1176
84
.
5.
Pietrement
C
,
Gorisse
L
,
Jaisson
S
,
Gillery
P
.
Chronic increase of urea leads to carbamylated proteins accumulation in tissues in a mouse model of CKD
.
PLoS One
.
2013
;
8
(
12
):
e82506
.
6.
Gorisse
L
,
Pietrement
C
,
Vuiblet
V
,
Schmelzer
CE
,
Kohler
M
,
Duca
L
et al
.
Protein carbamylation is a hallmark of aging
.
Proc Natl Acad Sci U S A
.
2016
;
113
(
5
):
1191
6
.
7.
Jaisson
S
,
Lorimier
S
,
Ricard-Blum
S
,
Sockalingum
GD
,
Delevallee-Forte
C
,
Kegelaer
G
et al
.
Impact of carbamylation on type I collagen conformational structure and its ability to activate human polymorphonuclear neutrophils
.
Chem Biol
.
2006
;
13
(
2
):
149
59
.
8.
Jaisson
S
,
Larreta-Garde
V
,
Bellon
G
,
Hornebeck
W
,
Garnotel
R
,
Gillery
P
.
Carbamylation differentially alters type I collagen sensitivity to various collagenases
.
Matrix Biol
.
2007
;
26
(
3
):
190
6
.
9.
Verbrugge
FH
,
Tang
WH
,
Hazen
SL
.
Protein carbamylation and cardiovascular disease
.
Kidney Int
.
2015
;
88
(
3
):
474
8
.
10.
Lim
K
,
Kalim
S
.
The role of nonenzymatic post-translational protein modifications in uremic vascular calcification
.
Adv Chronic Kidney Dis
.
2019
;
26
(
6
):
427
36
.
11.
Apostolov
EO
,
Shah
SV
,
Ok
E
,
Basnakian
AG
.
Carbamylated low-density lipoprotein induces monocyte adhesion to endothelial cells through intercellular adhesion molecule-1 and vascular cell adhesion molecule-1
.
Arterioscler Thromb Vasc Biol
.
2007
;
27
(
4
):
826
32
.
12.
Chen
Z
,
Ding
S
,
Wang
YP
,
Chen
L
,
Mao
JY
,
Yang
Y
et al
.
Association of carbamylated high-density lipoprotein with coronary artery disease in type 2 diabetes mellitus: carbamylated high-density lipoprotein of patients promotes monocyte adhesion
.
J Transl Med
.
2020
;
18
(
1
):
460
.
13.
Sakalihasan
N
,
Heyeres
A
,
Nusgens
BV
,
Limet
R
,
Lapiere
CM
.
Modifications of the extracellular matrix of aneurysmal abdominal aortas as a function of their size
.
Eur J Vasc Surg
.
1993
;
7
(
6
):
633
7
.
14.
Lu
H
,
Howatt
DA
,
Balakrishnan
A
,
Moorleghen
JJ
,
Rateri
DL
,
Cassis
LA
et al
.
Subcutaneous angiotensin II infusion using osmotic pumps induces aortic aneurysms in mice
.
J Vis Exp
.
2015
103
53191
.
15.
Doue
M
,
Okwieka
A
,
Berquand
A
,
Gorisse
L
,
Maurice
P
,
Velard
F
et al
.
Carbamylation of elastic fibers is a molecular substratum of aortic stiffness
.
Sci Rep
.
2021
;
11
(
1
):
17827
.
16.
Jaisson
S
,
Desmons
A
,
Doue
M
,
Gorisse
L
,
Pietrement
C
,
Gillery
P
.
Measurement of homocitrulline, A carbamylation-derived product, in serum and tissues by LC-MS/MS
.
Curr Protoc Protein Sci
.
2018
;
92
(
1
):
e56
.
17.
Battle
S
,
Gogonea
V
,
Willard
B
,
Wang
Z
,
Fu
X
,
Huang
Y
et al
.
The pattern of apolipoprotein A-I lysine carbamylation reflects its lipidation state and the chemical environment within human atherosclerotic aorta
.
J Biol Chem
.
2022
;
298
(
4
):
101832
.
18.
Ødegård
A
,
Aasland
J
,
Myhre
HO
,
Mollnes
TE
,
Videm
V
.
The inflammatory response to stent grafting of the thoracic aorta
.
Int Angiol
.
2007
;
26
(
3
):
219
27
.
19.
Kim
HW
,
Blomkalns
AL
,
Ogbi
M
,
Thomas
M
,
Gavrila
D
,
Neltner
BS
et al
.
Role of myeloperoxidase in abdominal aortic aneurysm formation: mitigation by taurine
.
Am J Physiol Heart Circ Physiol
.
2017
313
6
H1168
H1179
.
20.
Raaz
U
,
Zollner
AM
,
Schellinger
IN
,
Toh
R
,
Nakagami
F
,
Brandt
M
et al
.
Segmental aortic stiffening contributes to experimental abdominal aortic aneurysm development
.
Circulation
.
2015
;
131
(
20
):
1783
95
.
21.
Freestone
T
,
Turner
RJ
,
Coady
A
,
Higman
DJ
,
Greenhalgh
RM
,
Powell
JT
.
Inflammation and matrix metalloproteinases in the enlarging abdominal aortic aneurysm
.
Arterioscler Thromb Vasc Biol
.
1995
;
15
(
8
):
1145
51
.
22.
Apostolov
EO
,
Basnakian
AG
,
Ok
E
,
Shah
SV
.
Carbamylated low-density lipoprotein: nontraditional risk factor for cardiovascular events in patients with chronic kidney disease
.
J Ren Nutr
.
2012
;
22
(
1
):
134
8
.
23.
Santana
JM
,
Brown
CD
.
High-density lipoprotein carbamylation and dysfunction in vascular disease
.
Front Biosci
.
2018
;
23
(
12
):
2227
34
.
24.
Ok
E
,
Basnakian
AG
,
Apostolov
EO
,
Barri
YM
,
Shah
SV
.
Carbamylated low-density lipoprotein induces death of endothelial cells: a link to atherosclerosis in patients with kidney disease
.
Kidney Int
.
2005
;
68
(
1
):
173
8
.
25.
Holzer
M
,
Gauster
M
,
Pfeifer
T
,
Wadsack
C
,
Fauler
G
,
Stiegler
P
et al
.
Protein carbamylation renders high-density lipoprotein dysfunctional
.
Antioxid Redox Signal
.
2011
;
14
(
12
):
2337
46
.
26.
Mori
D
,
Matsui
I
,
Shimomura
A
,
Hashimoto
N
,
Matsumoto
A
,
Shimada
K
et al
.
Protein carbamylation exacerbates vascular calcification
.
Kidney Int
.
2018
;
94
(
1
):
72
90
.
27.
Chowienczyk
PJ
.
Aortic stiffness and disease: location is key
.
Circulation
.
2015
;
131
(
20
):
1745
7
.
28.
Malekzadeh
S
,
Fraga-Silva
RA
,
Trachet
B
,
Montecucco
F
,
Mach
F
,
Stergiopulos
N
.
Role of the renin-angiotensin system on abdominal aortic aneurysms
.
Eur J Clin Invest
.
2013
;
43
(
12
):
1328
38
.
You do not currently have access to this content.