Page 28 - GTM-2-1

Global Translational Medicine Stem cells in aortic aneurysm

associated with regression of inflammation and tissue fibroblasts. Recently, many types of cells have been found
repair. In addition, a large number of B lymphocytes and by applying single-cell transcriptomics in AA tissues.
T lymphocytes in AAA, with predominant CD4 T cells, In addition to endothelial cells, VSMCs and fibroblasts,
+
promoted AAA development by accumulating macrophages it has been found that AA also includes dendritic cells,
and regulating ECM and protease synthesis . In addition, monocytes, mast cells, and neutrophils from the intima to
[30]
neutrophils also contribute to the development of AAA. the adventitia. Figure 1 shows the approximate distribution
For example, IL-1β-induced neutrophil extracellular trap of those cells.
formation (NETosis) can lead to the formation of AAA . Although the etiology is different, cell damage,
[31]
2.3. TAA apoptosis and other inflammatory effects all contribute
to the formation of AAA and TAA. Therefore, before
Inherited diseases which mainly affect ECM and VSMC studying the pathophysiological mechanism of AAA and
are common causes of TAA. Three major reasons of the TAA, it is necessary to understand the type of cells that
formation of TAA and AAA are the same, but the specific are present and their basic characteristics. Single-cell
mechanism is slightly different. RNA sequencing with AAA and TAA tissues reveals the

Unique transcriptome-regulated VSMCs were presence of additional cell types, as shown in Table 1.
identified in AA tissues of adult Fbn1 C1041G/+ (MFS) mice,
and single-cell RNA sequencing of AA tissues from MFS 3. Stem cells
patients confirmed similar VSMC regulation, mainly In addition to the cells mentioned above, stem cells are
attributed to TGF-hanism is slight Krüppel-like factor 4 present in AA tissues as well. Stem cells have the potential
[32]
(Klf4) overexpression . VSMC contractile dysfunction to self-renew and differentiate into various cell types,
is also directly related to TAA. It was found that in the which not only involve in embryonic development but
thoracic aorta of AAD patients, the VSMC inflammasome also reside in adult tissue and can participate in tissue
NLRP3-caspase-1 cascade can degrade contractile repair by cell proliferation, migration, and differentiation
[33]
proteins, leading to VSMC contractile dysfunction . under various stimuli. Studies have shown that adult stem
A genetic imbalance of oxidative stress and ROS can cells and progenitor cells exist in the adult cardiovascular
trigger TAA. The mechanism of ROS imbalance is either system . Stem cells are also significant in the treatment
[49]
insufficient ROS removal or increased ROS production of AA.
due to the dysregulation of redox mediators . In addition,
[34]
oxidative stress inhibits autophagy in the MFS model, and 3.1. Endothelial progenitor cells
the autophagy mechanism plays a key role in regulating Bone marrow-derived endothelial progenitor cells (EPCs)
VSMC death and endoplasmic reticulum stress-dependent have the ability to differentiate into mature endothelial
inflammation, which has important effects on aortic wall cells and are involved in angiogenesis during the
homeostasis and repair . embryonic period, as well as endothelial cell turnover and
[35]
[50]
In molecular genetics, mutations in genes encoding local angiogenesis after adult vascular injury . Therefore,
various components of the TGF-β signaling cascade are EPCs are important for the development and treatment of
low
collectively referred to as TGF-β angiopathy (TGFβVs). AA. Typical markers include CD157, EPCR, and CD31
+
low
Mutations in genes encoding components of the smooth VEGFR2 IL33 Sox9 +[51] .
muscle contractile proteins (ACTA2, MYH11, MYLK, and The number of peripheral circulating EPCs in AAA
PRKG1) are thought to be the cause of smooth muscle patients was reduced and their function was impaired ,
[52]
vasoconstrictor disease . Mutations of the FBN1 gene but was increased significantly in TAA patients . Evidence
[36]
[53]
linking VSMC and ECM impair VSMC productivity, and also showed that the number of EPCs increases several
ACTA2 and MYH11 mutations cause disruption of the ATP- days after AA repair, possibly contributing to the rapid
dependent cyclic interaction, which, in turn, leads to VSMC endothelialization of blood vessels [54,55] . Current studies
productivity impairment. In addition, PRKG1 mutations have shown that in a rat AAA model, overexpressed nuclear-
result in kinase composition in the absence of cGMP. enriched abundant transcript 1 (NEAT1) competitively
Constitutive activation drives VSMC relaxation. Mutations binds to miR-204-5p and upregulates the expression
in the above genes all lead to the occurrence of TAA . of angiotensin (Ang) I in EPCs, thereby increasing the
[37]
number of EPCs in peripheral blood to promote cell
2.4. Cells in TAA and AAA
[56]
viability, migration, and tube formation in AAA .
In past years, it was believed that the blood vessel wall Chemokine CXCL12 overexpression promotes the growth
was mainly composed of endothelial cells, VSMCs, and of smooth muscle-like cells and the expression of VEGF

Volume 2 Issue 1 (2023) 3 https://doi.org/10.36922/gtm.v2i1.241