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Vascular Medicine (London, England) Jun 2024To date, PCSK9 inhibitors are well known for eliminating cardiac and cerebral artery ischemia events by lowering the serum lipid level. However, the pathophysiological...
BACKGROUND
To date, PCSK9 inhibitors are well known for eliminating cardiac and cerebral artery ischemia events by lowering the serum lipid level. However, the pathophysiological value of in-plaque PCSK9 expression is still unclear.
METHODS
Advanced plaques removed by carotid endarterectomy were sectioned and stained to identify the PCSK9 expression pattern and its co-expression with rupture-relevant markers. To investigate the correlation of PCSK9 expression with regional blood shear flow, hemodynamic characteristics were analyzed using computational fluid dynamics, and representative parameters were compared between PCSK9 positive and negative staining plaques. To explore this phenomenon in vitro, human aortic vascular smooth muscle cells were used to overexpress and knock down PCSK9. The impacts of PCSK9 modulations on mechanical sensor activity were testified by western blot and immunofluorescence. Real-time polymerase chain reaction was used to evaluate the transcription levels of downstream rupture-prone effectors.
RESULTS
PCSK9 distribution in plaque preferred cap and shoulder regions, residing predominantly in smooth muscle actin-positive cells. Cap PCSK9 expression correlated with fibrous cap thickness negatively and co-expressed with MMP-9, both pointing to the direction of plaque rupture. A hemodynamic profile indicated a rupture-prone feature of cap PCSK9 expression. In vitro, overexpression and knockdown of PCSK9 in human aortic vascular smooth muscle cells has positive modulation on mechanical sensor Yes-associated protein 1 (YAP) activity and transcription levels of its downstream rupture-prone effectors. Serial section staining verified in situ colocalization among PCSK9, YAP, and downstream effectors.
CONCLUSIONS
Cap PCSK9 possesses a biomarker for rupture risk, and its modulation may lead to a novel biomechanical angle for plaque interventions.
PubMed: 38860436
DOI: 10.1177/1358863X241252370 -
Circulation Research Jun 2024Cell phenotype switching is increasingly being recognized in atherosclerosis. However, our understanding of the exact stimuli for such cellular transformations and their...
BACKGROUND
Cell phenotype switching is increasingly being recognized in atherosclerosis. However, our understanding of the exact stimuli for such cellular transformations and their significance for human atherosclerosis is still evolving. Intraplaque hemorrhage is thought to be a major contributor to plaque progression in part by stimulating the influx of CD163 macrophages. Here, we explored the hypothesis that CD163 macrophages cause plaque progression through the induction of proapoptotic endothelial-to-mesenchymal transition (EndMT) within the fibrous cap.
METHODS
Human coronary artery sections from CVPath's autopsy registry were selected for pathological analysis. Athero-prone and mice were used for in vivo studies. Human peripheral blood mononuclear cell-induced macrophages and human aortic endothelial cells were used for in vitro experiments.
RESULTS
In 107 lesions with acute coronary plaque rupture, 55% had pathological evidence of intraplaque hemorrhage in nonculprit vessels/lesions. Thinner fibrous cap, greater CD163 macrophage accumulation, and a larger number of CD31/FSP-1 (fibroblast specific protein-1) double-positive cells and TUNEL positive cells in the fibrous cap were observed in nonculprit intraplaque hemorrhage lesions, as well as in culprit rupture sections versus nonculprit fibroatheroma sections. Human aortic endothelial cells cultured with supernatants from hemoglobin/haptoglobin-exposed macrophages showed that increased mesenchymal marker proteins (transgelin and FSP-1) while endothelial markers (VE-cadherin and CD31) were reduced, suggesting EndMT induction. Activation of NF-κB (nuclear factor kappa β) signaling by proinflammatory cytokines released from CD163 macrophages directly regulated the expression of Snail, a critical transcription factor during EndMT induction. Western blot analysis for cleaved caspase 3 and microarray analysis of human aortic endothelial cells indicated that apoptosis was stimulated during CD163 macrophage-induced EndMT. Additionally, deletion in athero-prone mice suggested that CD163 is required for EndMT and plaque progression. Using single-cell RNA sequencing from human carotid endarterectomy lesions, a population of EndMT was detected, which demonstrated significant upregulation of apoptosis-related genes.
CONCLUSIONS
CD163 macrophages provoke EndMT, which may promote plaque progression through fibrous cap thinning.
PubMed: 38860377
DOI: 10.1161/CIRCRESAHA.123.324082 -
Vascular Jun 2024Research on degenerative abdominal aortic aneurysms (AAA) is hampered by complex pathophysiology, sub-optimal pre-clinical models, and lack of effective medical... (Review)
Review
BACKGROUND
Research on degenerative abdominal aortic aneurysms (AAA) is hampered by complex pathophysiology, sub-optimal pre-clinical models, and lack of effective medical therapies. In addition, trustworthiness of existing epidemiological data is impaired by elements of ambiguity, inaccuracy, and inconsistency. Our aim is to foster debate concerning the trustworthiness of AAA epidemiological data and to discuss potential solutions.
METHODS
We searched the literature from the last five decades for relevant epidemiological data concerning AAA development, rupture, and repair. We then discussed the main issues burdening existing AAA epidemiological figures and proposed suggestions potentially beneficial to AAA diagnosis, prognostication, and management.
RESULTS
Recent data suggest a heterogeneous scenario concerning AAA epidemiology with rates markedly varying by country and study cohorts. Overall, AAA prevalence seems to be decreasing worldwide while mortality is apparently increasing regardless of recent improvements in aortic-repair techniques. Prevalence and mortality are decreasing in high-income countries, whereas low-income countries show an increase in both. However, several pieces of information are missing or outdated, thus systematic renewal is necessary. Current AAA definition and surgical criteria do not consider inter-individual variability of baseline aortic size, further decreasing their reliability.
CONCLUSIONS
Switching from flat aortic-size thresholds to relative aortic indices would improve epidemiological trustworthiness regarding AAAs. Aortometry standardization focusing on simplicity, univocity, and accuracy is crucial. A patient-tailored approach integrating clinical data, multi-adjusted indices, and imaging parameters is desirable. Several novel imaging modalities boast promising profiles for investigating the aortic wall. New contrast agents, computational analyses, and artificial intelligence-powered software could provide further improvements.
PubMed: 38842081
DOI: 10.1177/17085381241257747 -
Expert Review of Medical Devices Jun 2024Type A acute aortic dissection (TA-AAD) is a great challenge for aortic surgeons. The establishment of a standardized surgical approach, particularly the determination... (Review)
Review
INTRODUCTION
Type A acute aortic dissection (TA-AAD) is a great challenge for aortic surgeons. The establishment of a standardized surgical approach, particularly the determination of whether and when to address the aortic arch and the distal aorta in the same operation as the proximal aorta, is still unclear.
AREAS COVERED
Frozen elephant trunk (FET) has emerged as a valuable treatment for TA-AAD over the last decade. Here, we discuss the fundamentals and pitfalls of frozen elephant trunk procedures and present the latest innovations.
EXPERT OPINION
FET has the potential to simplify arch reconstruction in patients with complex arch tears and rupture, optimize perfusion in the distal true lumen for those with a compressed true lumen and malperfusion, address distal reentry tears, and promote false lumen thrombosis and late aortic remodeling. Nevertheless, FET is still associated with non-negligible mortality and morbidity rates. Patient selection, surgical expertise, and postoperative care remain crucial determinants in ensuring successful outcomes. Recent innovations in FET surgery involve the development of techniques to minimize or avoid hypothermic circulatory arrest and new FET devices with different arch branch configurations aiming to facilitate subsequent aortic reinterventions. We believe that both these advancements have the potential to improve patient outcomes.
PubMed: 38841791
DOI: 10.1080/17434440.2024.2365416 -
Surgery Jun 2024We aimed to analyze the feasibility of endovascular treatment for brucellosis-related aorta-iliac artery pseudoaneurysm. We did a statistical analysis that among the 11...
We aimed to analyze the feasibility of endovascular treatment for brucellosis-related aorta-iliac artery pseudoaneurysm. We did a statistical analysis that among the 11 cases, the thoracic aorta was involved in 3 cases, the abdominal aorta was involved in 6 cases, and the iliac artery was involved in 2 cases. Five patients had a history of contact with cattle and sheep, 3 had a history of drinking raw milk, 10 patients had a fever before the operation, and 11 patients had positive serum agglutination test. Blood culture was positive in 2 patients. All patients were given anti-brucellosis treatment immediately after diagnosis. One died of aortic rupture 5 days after emergency endovascular gastrointestinal bleeding. Endovascular-covered stent implantation and active anti-brucellosis therapy were used to treat 10 patients. The follow-up period was 8 years without aortic complications or death for all patients. We think early diagnosis and a combination of anti-brucellosis drugs and endovascular therapy may be the first choice for treating the pseudoaneurysm caused by Brucella.
PubMed: 38839433
DOI: 10.1016/j.surg.2024.04.032 -
Cardiovascular Research Jun 2024Abdominal aortic aneurysm (AAA) represents a life-threatening condition characterized by medial layer degeneration of the abdominal aorta. Nevertheless, knowledge...
AIMS
Abdominal aortic aneurysm (AAA) represents a life-threatening condition characterized by medial layer degeneration of the abdominal aorta. Nevertheless, knowledge regarding changes in regulators associated with aortic status remains incomplete. A thorough understanding of cell types and signaling pathways involved in the development and progression of AAAs is essential for the development of medical therapy.
METHODS AND RESULTS
We harvested specimens of the abdominal aorta with different pathological features in Angiotensin II (AngII)-infused ApoE-/- mice, conducted scRNA-seq, identified a unique population of interferon-inducible monocytes/macrophages (IFNICs), which were amply found in the abdominal aortic aneurysms (AAAs). Gene set variation analysis (GSVA) revealed that activation of the cytosolic DNA sensing cGAS-STING and JAK-STAT pathways promoted the secretion of type I interferons in monocytes/macrophages and differentiated them into IFNICs. We generated myeloid cell-specific deletion of Sting1 (Lyz2-Cre+/-; Sting1flox/flox) mice and performed bone marrow transplantation and found that myeloid cell-specific deletion of Sting1 or Ifnar1 significantly reduced the incidence of AAA, aortic rupture rate and diameter of the abdominal aorta. Mechanistically, the activated pyroptosis- and inflammation-related signaling pathways, regulated by IRF7 in IFNICs, play critical roles in the developing AAAs.
CONCLUSION
IFNICs is a unique monocyte/macrophage subset implicated in the development of AAAs and aortic rupture.
PubMed: 38836630
DOI: 10.1093/cvr/cvae117 -
Acta Medica Philippina 2024Ruptured Sinus of Valsalva (RSOV) is a rarely encountered cardiac anomaly that can potentially lead to adverse clinical outcomes. RSOV increases the risk of morbidity...
Ruptured Sinus of Valsalva (RSOV) is a rarely encountered cardiac anomaly that can potentially lead to adverse clinical outcomes. RSOV increases the risk of morbidity during pregnancy due to the physiological changes associated with gestation, that can exacerbate the underlying cardiac pathology. We present the case of a 29-year-old female with an uncorrected RSOV who required an emergency cesarean section for abruptio placenta. The patient underwent the procedure under spinal anesthesia, with careful titration of norepinephrine infusion and close monitoring of hemodynamic parameters using an invasive intra-arterial line. Given the absence of established anesthetic protocols for parturients with RSOV undergoing cesarean delivery, a comprehensive understanding of the complex interaction between the hemodynamic effects of RSOV, pregnancy, and anesthesia is essential. This understanding enables the safe use of spinal anesthesia in urgent situations, leading to favorable patient outcomes.
PubMed: 38836072
DOI: 10.47895/amp.v58i9.8746 -
Trauma Case Reports Jun 2024Hemorrhage is among the leading causes of death for trauma patients. Adjunct techniques used to control bleeding include use of aortic cross clamping, application of a...
The novel use of resuscitative endovascular balloon occlusion of the aorta for uncontrolled bleeding in a surgically inaccessible abdomen: The ruptured proper hepatic artery in a frozen abdomen.
Hemorrhage is among the leading causes of death for trauma patients. Adjunct techniques used to control bleeding include use of aortic cross clamping, application of a pelvic binder, rapidly expanding hemostatic sponges, and extra-peritoneal packing. Additionally, Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) can provide life-saving proximal control for patients with massive internal hemorrhage. This study concerns a patient treated with Zone 1 REBOA for class IV hemorrhagic shock from a spontaneous common hepatic artery rupture. REBOA was performed at bedside in the Surgical Intensive Care Unit (SICU) prior to definitive selective embolization. A healthy 28-year-old male suffered a grade 4 liver laceration and pancreatic head transection with associated duodenal injury after a high-speed motor vehicle collision. On arrival, the patient required a damage control laparotomy with multiple reoperations for management of his intra-abdominal injuries. By hospital day 11, significant visceral adhesions resulted in a frozen abdomen. On hospital day 20, the patient developed massive hematemesis, hematochezia, and class IV hemorrhagic shock. Vascular surgery was called to bedside in the SICU to perform REBOA. The patient received massive transfusion protocol while a 12 Fr sheath was inserted, and an aortic occlusion balloon was inflated in Zone 1 allowing for hemodynamic stabilization for transport and definitive management in the angiography suite. This case reports a novel use of REBOA, at bedside in the SICU, for the management of a massive gastrointestinal bleed in a patient with frozen abdomen. In this case, REBOA allowed us to achieve temporary hemodynamic stability prior to definitive control in the angiography suite. Bedside use of REBOA in the SICU prevented certain exsanguination and death.
PubMed: 38835529
DOI: 10.1016/j.tcr.2024.101002 -
Innovations (Philadelphia, Pa.) Jun 2024Induced hypothermia improves outcome in aortic arch surgery, neonatal neurointensive care, and transplant surgery for example. In contrast, spontaneous hypothermia has...
OBJECTIVE
Induced hypothermia improves outcome in aortic arch surgery, neonatal neurointensive care, and transplant surgery for example. In contrast, spontaneous hypothermia has been associated with worse outcomes in patients suffering from hemorrhagic shock, mostly explained by its adverse effects on the coagulation system. We investigated if induced hypothermia would impair short-term survival in experimental aortic rupture with retroperitoneal bleeding.
METHODS
Anesthetized pigs were randomized into 2 groups: hypothermia by peritoneal lavage of ice-cold Ringer's acetate and external cooling ( = 10) and normothermia ( = 10). Aortic rupture with retroperitoneal bleeding was induced by endovascular means creating a 6 mm hole in the retroperitoneal portion of abdominal aorta. Survival (primary outcome), hemodynamics, and arterial blood gases including lactate were collected and analyzed up to 180 min after aortic rupture.
RESULTS
The body temperature (mean ± standard deviation) in the hypothermic group was 31.5 ± 1.0 °C and 38.7 ± 0.4 °C in the normothermic group at the time for aortic rupture. Survival up to 180 min after the retroperitoneal bleeding was significantly higher in the hypothermic compared with the normothermic group ( = 0.023).
CONCLUSIONS
Induced hypothermia did not impair survival in this experimental retroperitoneal aortic bleeding model in anesthetized pigs. This finding may indicate a minor role for the coagulation system in this type of bleeding.
PubMed: 38828939
DOI: 10.1177/15569845241253234