Recent advances in targeted therapy for inflammatory vascular diseases.

Vascular diseases constitute a significant contributor to worldwide mortality rates, placing a substantial strain on healthcare systems and socio-economic aspects. They are closely associated with inflammatory responses, as sustained inflammation could impact endothelial function, the release of inflammatory mediators, and platelet activation, thus accelerating the progression of vascular diseases. Consequently, directing therapeutic efforts towards mitigating inflammation represents a crucial approach in the management of vascular diseases. Traditional anti-inflammatory medications may have extensive effects on multiple tissues and organs when absorbed through the bloodstream. Conversely, treatments targeting inflammatory vascular diseases, such as monoclonal antibodies, drug-eluting stents, and nano-drugs, can achieve more precise effects, including precise intervention, minimal non-specific effects, and prolonged efficacy. In addition, personalized therapy is an important development trend in targeted therapy for inflammatory vascular diseases. Leveraging advanced simulation algorithms and clinical trial data, treatment strategies are gradually being personalized based on patients' genetic, biomarker, and clinical profiles. It is expected that the application of precision medicine in the field of vascular diseases will have a broader future. In conclusion, targeting therapies offer enhanced safety and efficacy compared to conventional medications; investigating novel targeting therapies and promoting clinical transformation may be a promising direction in improving the prognosis of patients with inflammatory vascular diseases. This article reviews the pathogenesis of inflammatory vascular diseases and presents a comprehensive overview of the potential for targeted therapies in managing this condition.

Asiatic acid alleviates vascular remodeling in BAPN-induced aortic dissection through inhibiting NF-κB p65/CX3CL1 signaling.

Inflammation assumes a pivotal role in the aortic remodeling of aortic dissection (AD). Asiatic acid (AA), a triterpene compound, is recognized for its strong anti-inflammatory properties. Yet, its effects on ß-aminopropionitrile (BAPN)-triggered AD have not been clearly established. The objective is to determine whether AA attenuates adverse aortic remodeling in BAPN-induced AD and clarify potential molecular mechanisms. In vitro studies, RAW264.7 cells pretreated with AA were challenged with lipopolysaccharide (LPS), and then the vascular smooth muscle cells (VSMCs)-macrophage coculture system was established to explore intercellular interactions. To induce AD, male C57BL/6J mice at three weeks of age were administered BAPN at a dosage of 1 g/kg/d for four weeks. To decipher the mechanism underlying the effects of AA, RNA sequencing analysis was conducted, with subsequent validation of these pathways through cellular experiments. AA exhibited significant suppression of M1 macrophage polarization. In the cell coculture system, AA facilitated the transformation of VSMCs into a contractile phenotype. In the mouse model of AD, AA strikingly prevented the BAPN-induced increases in inflammation cell infiltration and extracellular matrix degradation. Mechanistically, RNA sequencing analysis revealed a substantial upregulation of CX3CL1 expression in BAPN group but downregulation in AA-treated group. Additionally, it was observed that the upregulation of CX3CL1 negated the beneficial impact of AA on the polarization of macrophages and the phenotypic transformation of VSMCs. Crucially, our findings revealed that AA is capable of downregulating CX3CL1 expression, accomplishing this by obstructing the nuclear translocation of NF-κB p65. The findings indicate that AA holds promise as a prospective treatment for adverse aortic remodeling by suppressing the activity of NF-κB p65/CX3CL1 signaling pathway.

Triglyceride-glucose index and triglyceride to high-density lipoprotein cholesterol ratio predict the prognosis in patients with type B aortic dissection receiving thoracic endovascular aortic repair.

Background: The triglyceride-glucose (TyG) index and triglyceride to high-density lipoprotein cholesterol (TG/HDL-c) ratio are both reliable surrogate indicator of insulin resistance and have been shown to be valuable in predicting various cardiovascular diseases. However, few studies have explored its association with the prognosis of type B aortic dissection (TBAD) patients receiving thoracic endovascular aortic repair (TEVAR). Methods: A total of 1,425 consecutive patients who underwent TEVAR were included. Data from 935 patients were analyzed in the study. The endpoint was defined as 30-day and 1-year aortic-related adverse events (ARAEs), all-cause mortality, and major adverse cardiovascular and cerebrovascular events (MACCEs). Results: There were 935 patients included during a mean follow-up time of 2.8 years. After adjusting for multiple confounding factors, continuous TG/HDL-c [hazard ratio (HR) =1.07; 95% confidence interval (CI): 1.00-1.15; P=0.041] was independently associated with 1-year all-cause mortality. Both a high (Quintile 5: TG/HDL-c ratio ≥4.11) (HR =4.84; 95% CI: 1.55-15.13; P=0.007) and low TG/HDL-c ratio (Quintile 1: TG/HDL-c ratio <1.44) (HR =4.67; 95% CI: 1.46-14.94; P=0.001) were still independent risk factors for 1-year all-cause mortality. Conclusions: Elevated baseline TG/HDL-c ratio and TG/HDL-c ≥4.11 were significantly related to a higher risk of 1-year all-cause mortality among TBAD patients undergoing TEVAR. At the same time, the low TG/HDL-c ratio was also independently associated with 1-year all-cause mortality. Special attention should be paid to TBAD patients with a higher or an overly low TG/HDL-c ratio.

Bibliometric analysis of monoclonal antibodies for atherosclerosis.

Atherosclerosis (AS) is a prevalent cardiovascular disease that greatly increases mortality in the aging population and imposes a heavy burden on global healthcare systems. The purpose of this study is to examine the research structure and current trends of monoclonal antibodies (mAbs) against AS from a bibliometric perspective, since the development of these drugs is currently booming. This study collected articles and reviews on mAbs against AS from the Web of Science Core Collection, spanning from 2003 to 2022. Biblioshiny was utilized to analyze and visualize the characteristics of countries, regions, authors, institutions, and journals included in this collection. We used VOS viewer to illustrate the frequency of country co-occurrence, and CiteSpace to visualize co-cited reference, keywords co-occurrence, keywords citation bursts, keywords clustering and timeline plots. The study included 1325 publications, with the United States emerging as a leading contributor to the field. ATHEROSCLEROSIS, CIRCULATION and ARTERIOSCLEROSISTHROMBOSIS AND VASCULAR BIOLOGY are core journals that publish high-quality literature on the latest advances in the field. Noteworthy authors with numerous high-quality publications include Witztum JL and Tsimikas S. Currently, lipid metabolism and inflammation are the main research areas of interest in this field. The mAbs against AS is an evolving field, and ongoing research continues to advance our understanding. This paper provides a comprehensive overview of the current state of knowledge in this area, highlighting two primary research directions: inflammation and lipid metabolism. Additionally, the paper identifies emerging research hotspots, which will provide researchers with useful insights to guide future investigations and anticipate research directions.

Senkyunolide I ameliorates thoracic aortic aneurysm and dissection in mice via inhibiting the oxidative stress and apoptosis of endothelial cells.

BACKGROUND: Thoracic aortic aneurysm and aortic dissection (TAAD) is one of the most fatal cardiovascular diseases. Senkyunolide I (SEI) is a component of traditional Chinese medicine with remarkable anti-inflammatory properties and exhibits remarkable protective effects, but its impact on TAAD remains unclear. Our study aimed to explore the role of SEI in a murine model of TAAD and further explore the immunopharmacological mechanism. METHODS AND MATERIALS: The in vivo model were assessed using echocardiography, gross anatomy, and tissue staining. Western blot and immunofluorescence were performed to evaluate the effects of SEI in vivo and in vitro. A SEI solution injection containing 1 % dimethyl sulfoxide (DMSO) was administered intraperitoneally to the TAAD model group, while a normal saline injection comprising 1 % DMSO was administered to the sham group. RESULTS: SEI prevented TAAD formation induced by BAPN/Ang II and reduced the TAAD incidence in mice. SEI treatment significantly inhibited the degradation of collagen and elastin fibers in the extracellular matrix. Furthermore, it reduced the expression of inflammatory factors in the aortic intima. Western blot analysis revealed that SEI-treated mice showed a significant decrease in apoptosis-related protein levels in the aorta compared with the TAAD group. PI3K, Akt, and mTOR in the SEI treatment group were significantly lower than in the model group. SEI could also attenuate H2O2-induced Human umbilical vein endothelial cells (HUVECs) damage and reverse the decline in migrant cells. The apoptosis of HUVECs was considerably reduced by the SEI treatment. CONCLUSIONS: Conclusively, SEI may alleviate the progression of TAAD by suppressing the PI3K/Akt/NF-κB signaling pathway. The SEI's ability to inhibit inflammation and oxidative stress opens the way to restore the function of endothelial cells and vascular homeostasis, and thus to provide novel and promising options for the treatment of TAAD patients.

The intervention seasons of thoracic endovascular aortic repair impacted the outcomes for patients with type B aortic dissection.

Purpose: The objective of this research was to investigate whether seasonal variations influence the outcomes of type B aortic dissection (TBAD) patients with thoracic endovascular aortic repair (TEVAR). Patients and methods: From 2003 to 2020, a retrospective cohort study was performed, which included 1,123 TBAD patients who received TEVAR. Medical records were used to gather data on baseline characteristics. Outcomes including all-cause mortality and aortic-related adverse events (ARAEs) were tracked and analyzed. Results: Of the 1,123 TBAD patients in this study, 308 received TEVAR in spring (27.4%), 240 cases in summer (21.4%), 260 cases in autumn (23.2%), and 315 cases in winter (28.0%). Patients in the autumn group had a significantly lower risk of 1-year mortality than those in the spring group (hazard ratio: 2.66, 95% confidence interval: 1.06-6.67, p = 0.037). Kaplan-Meier curves revealed that patients who underwent TEVAR in autumn had a lower risk of 30-day ARAEs (p = 0.049) and 1-year mortality (p = 0.03) than those in spring. Conclusion: This study confirmed that TEVAR operated in autumn for TBAD was associated with a lower risk of 30-day ARAEs and 1-year mortality than in spring.

Peripheral Eosinophil Count Is Associated With the Prognosis of Patients With Type B Aortic Dissection Undergoing Endovascular Aortic Repair: A Retrospective Cohort Study.

Background Eosinophil count (EOS) has been proposed to provide prognostic information in multiple cardiovascular disorders. However, few researchers have investigated the predictive value of EOS for patients with type B aortic dissection who had thoracic endovascular repair. Methods and Results The authors reviewed the records of 912 patients with type B aortic dissection who were treated with thoracic endovascular repair in Changhai Hospital, Shanghai. By using receiver operating characteristic curve analysis, patients were divided into 2 groups based on the admission EOS cutoff value (<7.4×106/L [n=505] and ≥7.4×106/L [n=407]). To reduce selection bias, propensity score matching was applied. Multivariable regression analysis and Kaplan-Meier curves were performed to assess the association between EOS and long-term outcomes. Furthermore, we investigated nonlinear correlations between EOS and outcomes using general additive models with restricted cubic splines. In the matched population, lower EOS was associated with significantly higher 30-day mortality (4.1% vs 0%, P=0.007). There was no statistically difference in 30-day adverse events between the 2 groups (all P>0.05). Kaplan-Meier analysis revealed that patients with an EOS <7.4×106/L had a higher incidence of 1-year all-cause death (7.95% vs. 2.34%, P=0.008) and aortic-related death (5.98% vs 1.81%, P=0.023) than those with higher EOS. Multivariable Cox analysis showed that continuous EOS was independently associated with 1-year mortality (hazard ratio, 3.23 [95% CI, 1.20-8.33], P=0.019). In addition, we discovered a nonlinear association between EOS and 1-year outcomes. Conclusions Lower admission EOS values predict higher short- and long-term mortality after thoracic endovascular repair.

Elevated Admission Cardiac Troponin I Predicts Adverse Outcomes of Acute Type B Aortic Dissection after Endovascular Treatment.

Background: There is a lack of evidence about the predictive role of serum cardiac troponin I (cTnI) on the long-term adverse outcomes of acute type B aortic dissection (aTBAD) patients after thoracic endovascular aortic repair (TEVAR). In this study, we identified whether cTnI was an independent risk factor of 5-year adverse outcomes for aTBAD patients after TEVAR. Methods: We reviewed consecutive aTBAD patients without previous heart disease who were admitted for TEVAR. The total study population was divided into the cTnI(+) group (≥0.03 ng/mL) and the cTnI(-) group (<0.03 ng/mL) according to the time-dependent receiver operating characteristic curve analysis. The differences in clinical characteristics, operative details and clinical outcomes were compared between the two groups. Results: There was no difference in age and male prevalence between the two groups. Compared with the cTnI(-) group, the incidence of chronic kidney disease was higher in patients with cTnI ≥0.03 ng/mL. In addition, the cTnI(+) group presented with more frequent premature beats and non-myocardial-infarction ST-T segment changes. In terms of laboratory examinations, white blood cell counts, neutrophil counts, serum D-dimer and serum fibrin degradation products showed an increase in the cTnI(+) group, while lymphocyte and platelet counts showed a decrease in these patients. Patients with elevated cTnI suffered from increased risks of 5-year aortic-related adverse events (hazard ratio, HR = 1.822, 95% confidence interval, CI: 1.094-3.035; p = 0.021) and all-cause mortality (HR = 4.009, 95% CI: 2.175-7.388; p < 0.001). Conclusion: Among aTBAD patients without previous heart disease, preoperative elevated cTnI identified patients at an increased risk of long-term adverse outcomes after TEVAR.

Long-Term Outcomes of Endovascular Treatment for Type B Aortic Dissection with Simple Renal Cysts: A Multicenter Retrospective Study.

Background: Few studies have investigated the characteristics and long-term outcomes of type B aortic dissection (BAD) patients with simple renal cysts (SRC) after thoracic endovascular aortic repair (TEVAR). Methods: A multi-center retrospective cohort study was performed, including 718 BAD patients undergoing TEVAR from 2003 to 2016. The prevalence of SRC was 34.5% (n = 248). After propensity score matching, 214 matched pairs were selected for further analysis. Primary outcomes were long-term aortic-related adverse events (ARAEs). The effects of SRC in each subgroup of interest and their interactions were analyzed. Results: BAD patients with SRC were older and had a greater prevalence of comorbidities, including hypertension, coronary artery disease and chronic occlusive pulmonary disease. In addition, the SRC group presented a greater proportion of pleural effusion and aortic calcification. Compared with the non-SRC group, a significantly higher maximal diameter of ascending aorta was observed in the SRC group. Apart from the timing of the operation, no differences were found in the medication regime or intra-operative parameters. In the matched population, patients with SRC were at a higher risk of ARAEs in the long term. The multivariable Cox model indicated that SRC was an independent predictor of long-term ARAEs (hazard ratio: 1.84, 95% confidence interval: 1.13-3.00). The interaction between SRC and hypertension on rupture after TEVAR was statistically significant (p = 0.023). Conclusions: Compared with the non-SRC group, BAD patients with SRC experienced a higher risk of long-term ARAEs after TEVAR. Among the SRC subgroup, hypertensive patients had the highest risk of rupture after TEVAR.

Long-term results of type B aortic dissection patients with tumor after endovascular repair or optimal medical therapy: a single-center and retrospective cohort study.

BACKGROUND: The effect of thoracic endovascular aortic repair (TEVAR) for acute Type B aortic has been confirmed, However, when patients with malignant disease suffer from acute type B aortic dissection (ATBAD), the effect of TEVAR intervention is still unclear. METHODS: ATBAD patients were identified from electronic medical records between 2009 and 2019. The 5 year overall and aortic-disease free survival rates were analyzed and compared between the two groups. RESULTS: Of the 40 enrolled patients, 27 (67.5%) received TEVAR and 13 (32.5%) received OMT. The baseline characteristics of the two groups were not significantly different. Kaplan‒Meier survival curve showed that the 5 year overall survival and 5 year aortic-disease free survival of the TEVAR group were better than those of the OMT group. The Cox proportional hazard model with unadjusted risk showed an 83.0% decrease in 5 year overall mortality (HR, 0.17; 95% CI, 0.05-0.56) and a lower aortic-disease related risk (HR, 0.08; 95% CI, 0.02-0.39) in TEVAR group compared to OMT group. After adjusted for age, gender, smoking, drinking and comorbidities (diabetes mellitus, hypertension and coronary artery diseases), the hazard ratio of 5 year overall mortality was 78.0% lower (HR, 0.22; 95% CI, 0.06.0.81) and the risk of aortic-disease related mortality was 93.0% lower (HR, 0.07; 95% CI, 0.01-0.61) in TEVAR group compared to OMT group. In the cohort stratified by age, sex, the risk of the 5 year overall or aortic-disease related mortality in TEVAR group was relatively reduced compared to OMT group. CONCLUSIONS: Compared to OMT, TEVAR improves the 5 year overall and aortic-disease free survival rates in the cohort of ATBAD patients with a single type of malignant tumors.

Generation of ice states through deep reinforcement learning.

We present a deep reinforcement learning framework where a machine agent is trained to search for a policy to generate a ground state for the square ice model by exploring the physical environment. After training, the agent is capable of proposing a sequence of local moves to achieve the goal. Analysis of the trained policy and the state value function indicates that the ice rule and loop-closing condition are learned without prior knowledge. We test the trained policy as a sampler in the Markov chain Monte Carlo and benchmark against the baseline loop algorithm. This framework can be generalized to other models with topological constraints where generation of constraint-preserving states is difficult.