Targeting Platelet Activation in Abdominal Aortic Aneurysm: Current Knowledge and Perspectives
Abstract
:1. Introduction
2. Methods
3. Results
3.1. Study Selection
3.2. Platelets and Vascular Hemostasis
3.3. Role of Platelets in AAA
3.3.1. Low Platelet Count in AAA
3.3.2. Platelet-Aggregating Thrombus in AAA
3.4. Platelet Receptors in AAA
3.4.1. Adenosine Diphosphate Receptors
3.4.2. P-Selectin
3.4.3. Other Receptors
Target | Inhibitor | Disease Model | Study Type | Main Findings | Reference |
---|---|---|---|---|---|
ADP receptor | P2Y12 receptor antagonist AZD6140 | Decellularized aortic xenograft model of AAA in rats | Animal study | Reduced the spontaneous increase in aortic diameter | [42] |
ADP receptor | Clopidogrel | Apolipoprotein E-knockout mice infused with Ang II (AAA model) | Animal study | Suppressed aneurysm formation | [43] |
ADP receptor | Clopidogrel bisulfate | Hypercholesterolemic mice infused with Ang II (AAA model) | Animal study | Reduced AAA rupture | [44] |
ADP receptor | Clopidogrel bisulfate, ticagrelor, or prasugrel | Patients with AAA who progressed to rupture or dissection | Cohort study | Reduced rupture and dissection | [44] |
ADP receptor | Ticagrelor | Patients with AAA and a maximum aorta diameter of 35–49 mm | Multicenter randomized controlled trial | No reduction in growth of small AAA | [45] |
P-selectin | — | Patients with AAA before surgery | Cohort study | Soluble P-selectin significantly increased in plasma | [36] |
P-selectin | — | Decellularized aortic xenograft model of AAA in rats | Animal study | Soluble P-selectin significantly increased in rats | [36] |
P-selectin | Global knockout | P-selectin knockout mice with elastase perfusion (AAA model) | Animal study | P-selectin deficiency attenuated aneurysm formation | [47] |
P-selectin | Global PSGL-1 knockout | Aortic aneurysm model induced by deoxycorticosterone acetate plus high salt | Animal study | Reduced the incidence and severity of aortic aneurysm | [48] |
αIIbβ3 | αIIbβ3 inhibitor abciximab | Decellularized aortic xenograft model of AAA in rats | Animal study | Reduced thrombus area and aneurysmal enlargement | [36] |
GPIb | — | Patients with asymptomatic AAA | Case-control study | Higher glycocalicin produced by cleaved GPIb than normal population | [26] |
3.5. Platelet-Derived Mediators in AAA
3.5.1. TxA2
3.5.2. PDGF
3.5.3. CD40L-CD40
3.5.4. Platelet Factor 4 (PF4/CXCL4) and RANTES (CCL5)
3.5.5. Other Mediators
Target | Inhibitor | Disease Model | Study Type | Main Findings | Reference |
---|---|---|---|---|---|
TxA2 | TxA2 inhibitor BM-573 | AAA model in rats | Animal study | Suppressed aneurysmal growth | [53] |
TxA2 | Aspirin | Ang II infusion in hypercholesterolemic mice (AAA model) | Animal study | Reduced rupture | [44] |
PDGFA | — | Patients with AAA | Cohort study | Increased in AAA tissue | [57] |
PDGFA, PDGFB | — | Patients with AAA | Cohort study | Stained on small vessels in aneurysmal walls | [58] |
PDGFD | — | Ang II-infused obese mice (AAA model) | Animal study | Inhibition in PDGFD function significantly reduced the incidence of AAA | [59] |
CD40L | CD40L global knockout | Ang II infusion (AAA model) | Animal study | Developed fewer aneurysms | [64] |
PF4 and RANTES | — | Patients with AAA | Cohort study | Involved in attracting neutrophils to the luminal layer of AAA specimens | [66] |
PF4 and RANTES | MKEY, peptide inhibitor of CXCL4-CCL5 | Transient infrarenal aortic porcine pancreatic elastase infusion in mice (AAA model) | Animal study | Reduced aortic diameter enlargement | [67] |
Ficolin-3 | — | Patients with AAA | Cohort study | Increased from activated platelets and AAA tissue | [69] |
PF4 and myeloperoxidase | — | Decellularized aortic xenograft model in rats (AAA model) | Animal study | Elevated in experimental saccular aneurysm compared with fusiform aneurysm | [70,71] |
vWF | — | Patients with AAA | Cohort study | Elevated pre- and postoperatively, decreased intraoperatively | [73] |
14-3-3ζ | — | Patients with AAA | Cohort study | Elevated in sections of AAA specimens | [74] |
Thrombospondin-1 and clusterin | — | Patients with AAA | Cohort study | Negatively associated with AAA patients in serum | [75] |
3.6. Platelet Activation and Hemodynamic Changes in AAA
3.7. Clinical Applications Related to Platelets in AAA
3.7.1. Labeled Platelets and Visualization Methods
3.7.2. Platelets and Surgical Interventions
3.7.3. Platelet Infusion and Perioperative Period
4. Concluding Remarks and Future Perspectives
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
AAA | abdominal aortic aneurysm |
ADP | adenosine diphosphate |
Ang II | angiotensin II |
COX-1 | cyclooxygenase 1 |
EVAR | endovascular aortic aneurysm repair |
GP | glycoprotein |
ILT | intra-luminal thrombus |
MMP | matrix metalloproteinase |
PDGF | platelet-derived growth factor |
PF4 | platelet factor 4 |
PSGL-1 | P-selectin glycoprotein ligand-1 |
TP | thromboxane prostanoid |
TxA2 | thromboxane A2 |
vWF | von Willebrand factor |
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Sun, W.; Zheng, J.; Gao, Y. Targeting Platelet Activation in Abdominal Aortic Aneurysm: Current Knowledge and Perspectives. Biomolecules 2022, 12, 206. https://doi.org/10.3390/biom12020206
Sun W, Zheng J, Gao Y. Targeting Platelet Activation in Abdominal Aortic Aneurysm: Current Knowledge and Perspectives. Biomolecules. 2022; 12(2):206. https://doi.org/10.3390/biom12020206
Chicago/Turabian StyleSun, Weiliang, Jingang Zheng, and Yanxiang Gao. 2022. "Targeting Platelet Activation in Abdominal Aortic Aneurysm: Current Knowledge and Perspectives" Biomolecules 12, no. 2: 206. https://doi.org/10.3390/biom12020206
APA StyleSun, W., Zheng, J., & Gao, Y. (2022). Targeting Platelet Activation in Abdominal Aortic Aneurysm: Current Knowledge and Perspectives. Biomolecules, 12(2), 206. https://doi.org/10.3390/biom12020206