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Scientific Reports Jun 2024Sepsis, marked by organ dysfunction, necessitates reliable biomarkers. Ribonuclease inhibitor 1 (RNH1), a ribonuclease (RNase) inhibitor, emerged as a potential...
Sepsis, marked by organ dysfunction, necessitates reliable biomarkers. Ribonuclease inhibitor 1 (RNH1), a ribonuclease (RNase) inhibitor, emerged as a potential biomarker for acute kidney injury and mortality in thoracoabdominal aortic aneurysm patients. Our study investigates RNH1 dynamics in sepsis, its links to mortality and organ dysfunction, and the interplay with RNase 1 and RNase 5. Furthermore, we explore RNH1 as a therapeutic target in sepsis-related processes like inflammation, non-canonical inflammasome activation, and iron homeostasis. We showed that RNH1 levels are significantly higher in deceased patients compared to sepsis survivors and correlate with creatine kinase, aspartate and alanine transaminase, bilirubin, serum creatinine and RNase 5, but not RNase 1. RNH1 mitigated LPS-induced TNFα and RNase 5 secretion, and relative mRNA expression of ferroptosis-associated genes HMOX1, FTH1 and HAMP in PBMCs. Monocytes were identified as the predominant type of LPS-positive PBMCs. Exogenous RNH1 attenuated LPS-induced CASP5 expression, while increasing IL-1β secretion in PBMCs and THP-1 macrophages. As RNH1 has contradictory effects on inflammation and non-canonical inflammasome activation, its use as a therapeutic agent is limited. However, RNH1 levels may play a central role in iron homeostasis during sepsis, supporting our clinical observations. Hence, RNH1 shows promise as biomarkers for renal and hepatic dysfunction and hepatocyte injury, and may be useful in predicting the outcome of septic patients.
Topics: Humans; Sepsis; Biomarkers; Iron; Homeostasis; Inflammation; Male; Female; Middle Aged; Aged; Inflammasomes; Lipopolysaccharides; THP-1 Cells; Carrier Proteins
PubMed: 38951571
DOI: 10.1038/s41598-024-65778-8 -
Thrombosis and Haemostasis Jul 2024Hereditary aortic diseases (hADs) increase the risk of aortic dissections and ruptures. Recently, we have established an objective approach to measure the rupture...
OBJECTIVE
Hereditary aortic diseases (hADs) increase the risk of aortic dissections and ruptures. Recently, we have established an objective approach to measure the rupture force of the murine aorta, thereby explaining the outcomes of clinical studies and assessing the added value of approved drugs in vascular Ehlers-Danlos syndrome (vEDS). Here, we applied our approach to six additional mouse hAD models.
MATERIAL AND METHODS
We used two mouse models ( and ) of Marfan syndrome (MFS) as well as one smooth-muscle-cell-specific knockout (SMKO) of and three CRISPR/Cas9-engineered knock-in models (, , and ). One of the two MFS models was subjected to 4-week-long losartan treatment. Per mouse, three rings of the thoracic aorta were prepared, mounted on a tissue puller, and uniaxially stretched until rupture.
RESULTS
The aortic rupture force of the SMKO and both MFS models was significantly lower compared with wild-type mice but in both MFS models higher than in mice modeling vEDS. In contrast, the , , and knock-in models presented no impaired aortic integrity. As expected, losartan treatment reduced aneurysm formation but surprisingly had no impact on the aortic rupture force of our MFS mice.
CONCLUSION
Our read-out system can characterize the aortic biomechanical integrity of mice modeling not only vEDS but also related hADs, allowing the aortic-rupture-force-focused comparison of mouse models. Furthermore, aneurysm progression alone may not be a sufficient read-out for aortic rupture, as antihypertensive drugs reducing aortic dilatation might not strengthen the weakened aortic wall. Our results may enable identification of improved medical therapies of hADs.
PubMed: 38950604
DOI: 10.1055/s-0044-1787957 -
Circulation Jul 2024
Topics: Aortic Aneurysm, Abdominal; Humans; Animals
PubMed: 38950116
DOI: 10.1161/CIRCULATIONAHA.124.069916 -
Scandinavian Cardiovascular Journal :... Dec 2024Acute Type A Aortic Dissection (AAAD) is one of the most life-threatening diseases, often associated with transient hyperglycemia induced by acute physiological stress....
BACKGROUND
Acute Type A Aortic Dissection (AAAD) is one of the most life-threatening diseases, often associated with transient hyperglycemia induced by acute physiological stress. The impact of stress-induced hyperglycemia on the prognosis of ST-segment elevation myocardial infarction has been reported. However, the relationship between stress-induced hyperglycemia and the prognosis of AAAD patients remains uncertain.
METHODS
The clinical data of 456 patients with acute type A aortic dissection were retrospectively reviewed. Patients were divided into two groups based on their admission blood glucose. Cox model regression analysis was performed to assess the relationship between stress-induced hyperglycemia and the 30-day and 1-year mortality rates of these patients.
RESULTS
Among the 456 patients, 149 cases (32.7%) had AAAD combined with stress-induced hyperglycemia (SIH). The results of the multifactor regression analysis of the Cox model indicated that hyperglycemia (RR = 1.505, 95% CI: 1.046-2.165, = 0.028), aortic coarctation involving renal arteries (RR = 3.330, 95% CI: 2.237-4.957, < 0.001), aortic coarctation involving superior mesenteric arteries (RR = 1.611, 95% CI: 1.056-2.455, = 0.027), and aortic coarctation involving iliac arteries (RR = 2.034, 95% CI: 1.364-3.035, = 0.001) were independent influences on 1-year postoperative mortality in AAAD patients.
CONCLUSION
The current findings indicate that stress-induced hyperglycemia measured on admission is strongly associated with 1-year mortality in patients with AAAD. Furthermore, stress-induced hyperglycemia may be related to the severity of the condition in patients with AAAD.
Topics: Humans; Retrospective Studies; Aortic Dissection; Male; Female; Hyperglycemia; Middle Aged; Time Factors; Risk Factors; Aged; Blood Glucose; Aortic Aneurysm; Risk Assessment; Acute Disease; Biomarkers; Prognosis; Adult
PubMed: 38949610
DOI: 10.1080/14017431.2024.2373099 -
BioRxiv : the Preprint Server For... Jun 2024Oxidative stress is implicated in the pathogenesis and progression of abdominal aortic aneurysm (AAA). Antioxidant delivery as a therapeutic for AAA is of substantial...
BACKGROUND
Oxidative stress is implicated in the pathogenesis and progression of abdominal aortic aneurysm (AAA). Antioxidant delivery as a therapeutic for AAA is of substantial interest although clinical translation of antioxidant therapy has met with significant challenges due to limitations in achieving sufficient antioxidant levels at the site of AAA. We posit that nanoparticle-based approaches hold promise to overcome challenges associated with systemic administration of antioxidants.
METHODS
We employed a peptide-based nanoplatform to overexpress a key modulator of oxidative stress, superoxide dismutase 2 (SOD2). The efficacy of systemic delivery of SOD2 mRNA as a nanotherapeutic agent was studied in two different murine AAA models. Unbiased mass spectrometry-enabled proteomics and high-dimensional bioinformatics were used to examine pathways modulated by SOD2 overexpression.
RESULTS
The murine SOD2 mRNA sequence was mixed with p5RHH, an amphipathic peptide capable of delivering nucleic acids to form self-assembled nanoparticles of ∼55 nm in diameter. We further demonstrated that the nanoparticle was stable and functional up to four weeks following self-assembly when coated with hyaluronic acid. Delivery of SOD2 mRNA mitigated the expansion of small AAA and largely prevented rupture. Mitigation of AAA was accompanied by enhanced SOD2 protein expression in aortic wall tissue. Concomitant suppression of nitric oxide, inducible nitric oxide synthase expression, and cell death was observed. Proteomic profiling of AAA tissues suggests that SOD2 overexpression augments levels of microRNAs that regulate vascular inflammation and cell apoptosis, inhibits platelet activation/aggregation, and downregulates mitogen-activated protein kinase signaling. Gene set enrichment analysis shows that SOD2 mRNA delivery is associated with activation of oxidative phosphorylation, lipid metabolism, respiratory electron transportation, and tricarboxylic acid cycle pathways.
CONCLUSIONS
These results confirm that SOD2 is key modulator of oxidative stress in AAA. This nanotherapeutic mRNA delivery approach may find translational application in the medical management of small AAA and the prevention of AAA rupture.
PubMed: 38948794
DOI: 10.1101/2024.06.17.599454 -
World Journal of Experimental Medicine Jun 2024Aortic aneurysm (AA) refers to the persistent dilatation of the aorta, exceeding three centimeters. Investigating the pathophysiology of this condition is important for... (Review)
Review
Aortic aneurysm (AA) refers to the persistent dilatation of the aorta, exceeding three centimeters. Investigating the pathophysiology of this condition is important for its prevention and management, given its responsibility for more than 25000 deaths in the United States. AAs are classified based on their location or morphology. various pathophysiologic pathways including inflammation, the immune system and atherosclerosis have been implicated in its development. Inflammatory markers such as transforming growth factor β, interleukin-1β, tumor necrosis factor-α, matrix metalloproteinase-2 and many more may contribute to this phenomenon. Several genetic disorders such as Marfan syndrome, Ehler-Danlos syndrome and Loeys-Dietz syndrome have also been associated with this disease. Recent years has seen the investigation of novel management of AA, exploring the implication of different immune suppressors, the role of radiation in shrinkage and prevention, as well as minimally invasive and newly hypothesized surgical methods. In this narrative review, we aim to present the new contributing factors involved in pathophysiology of AA. We also highlighted the novel management methods that have demonstrated promising benefits in clinical outcomes of the AA.
PubMed: 38948412
DOI: 10.5493/wjem.v14.i2.91408 -
Cureus May 2024This study highlights a case of late open conversion repair (OCR) for persistent Type II endoleak after endovascular aneurysm repair (EVAR), presenting a 78-year-old...
This study highlights a case of late open conversion repair (OCR) for persistent Type II endoleak after endovascular aneurysm repair (EVAR), presenting a 78-year-old male with a history of EVAR for an infrarenal abdominal aortic aneurysm. Despite conservative management of the initial endoleak, the aneurysm sac's progressive growth necessitated open reconstruction to salvage the graft. Successful postoperative outcomes emphasize the critical need for meticulous intervention strategies and surveillance in managing persistent Type II endoleaks. This case underlines the importance of a tailored approach, leveraging both endovascular and open surgical techniques, to optimize long-term outcomes and prevent aneurysm rupture in complex cases.
PubMed: 38947720
DOI: 10.7759/cureus.61420 -
Cureus Jun 2024Psoriasis is a chronic immune-mediated disease affecting the skin, nails, and/or joints. It is associated with systemic inflammation and may also be linked to an... (Review)
Review
Psoriasis is a chronic immune-mediated disease affecting the skin, nails, and/or joints. It is associated with systemic inflammation and may also be linked to an increased risk of atherosclerotic cardiovascular disease (ASCVD). The objectives of this study were to determine the overall risk of ASCVD in patients with psoriasis and to evaluate the risk according to ASCVD type and the severity of psoriasis. This was a systematic review and meta-analysis of observational studies reporting the association between psoriasis and one or more of the clinical types of ASCVD. We searched Medical Literature Analysis and Retrieval System Online (MEDLINE) via PubMed, Excerpta Medica Database (EMBASE), Scopus, Bielefeld Academic Search Engine (BASE), and Google Scholar for relevant studies in the English language from the beginning of their records to July 2023. Study selection and data extraction were conducted by four independent reviewers. A total of 21 observational studies (three cross-sectional, one case-control, and 17 cohort) were included in this review, representing a total of 778,049 patients with psoriasis and 16,881,765 control subjects without psoriasis. The included studies had varying degrees of covariate adjustment, and thus, their findings may have been subject to residual confounding. All the meta-analyses used the adjusted effect sizes and were based on the random-effects model. However, the cohort studies were analysed separately from the non-cohort studies (the case-control and cross-sectional studies). There was a significant association between psoriasis and ASCVD (cohort studies: hazard ratio (HR), 1.21; 95% confidence interval (CI), 1.14 to 1.28; I = 63%; p < 0.001; non-cohort studies: odds ratio (OR), 1.60; 95% CI, 1.34 to 1.92; I = 31%; p = 0.23). Psoriasis was also significantly associated with myocardial infarction (cohort studies: HR, 1.20; 95% CI, 1.10 to 1.31; I = 60%; p < 0.001; non-cohort studies: OR, 1.57; 95% CI, 1.15 to 2.15; I = 74%; p = 0.05), coronary artery disease (cohort studies: HR, 1.20; 95% CI, 1.13 to 1.28; I = 67%; p < 0.001; non-cohort studies: OR, 1.60; 95% CI, 1.34 to 1.92; I = 31%; p = 0.23), aortic aneurysm (HR, 1.45; 95% CI, 1.04 to 2.02; I = 67%; p = 0.08) but not with ischaemic stroke (HR, 1.14; 95% CI, 0.96 to 1.36; I = 44%; p = 0.17). Pooled analysis in terms of the severity of psoriasis showed that both mild (cohort studies: HR, 1.17; 95% CI, 1.08 to 1.26; I = 74%; p < 0.001; non-cohort studies: OR, 1.54; 95% CI, 1.25 to 1.90; I = 0%; p = 0.50) and severe (cohort studies: HR, 1.43; 95% CI, 1.23 to 1.65; I = 65%; p < 0.001; non-cohort studies: OR, 1.65; 95% CI, 1.29 to 2.12; I = 25%; p = 0.26) psoriasis were significantly associated with ASCVD. Psoriasis (including mild and severe disease) is associated with an increased risk of ASCVD, including coronary artery disease (CAD) and aortic aneurysm (AA). ASCVD risk assessment and prevention should be prioritised in all adult psoriasis patients. Future observational studies investigating the association between psoriasis and ASCVD should conduct a more comprehensive adjustment of covariates.
PubMed: 38947134
DOI: 10.7759/cureus.63379 -
Echocardiography (Mount Kisco, N.Y.) Jul 2024A rare transthoracic echocardiographic image of left sinus of Valsalva aneurysm complicated by thrombus formation.
A rare transthoracic echocardiographic image of left sinus of Valsalva aneurysm complicated by thrombus formation.
Topics: Humans; Sinus of Valsalva; Thrombosis; Aortic Aneurysm; Echocardiography; Male; Diagnosis, Differential
PubMed: 38946156
DOI: 10.1111/echo.15875 -
Physiological Reports Jul 2024The aim of this study was to identify risk factors for abdominal aortic aneurysm (AAA) from the largest Welsh screening cohort to date. Patients were recruited from...
The aim of this study was to identify risk factors for abdominal aortic aneurysm (AAA) from the largest Welsh screening cohort to date. Patients were recruited from 1993 (to 2015) as part of the South East Wales AAA screening programme through general practitioners. Demographic data and risk factors were collected by means of a self-report questionnaire. Statistical tests were performed to determine whether associations could be observed between AAA and potential risk factors. Odds ratios (OR) were also calculated for each of the risk factors identified. A total of 6879 patients were included in the study. Two hundred and seventy-five patients (4.0%) presented with AAA, of which 16% were female and 84% were male. Patients with AAA were older than the (no AAA) control group (p < 0.0001). The following risk factors were identified for AAA: family history of AAA (p < 0.0001); history of vascular surgery (p < 0.0001), cerebrovascular accident (p < 0.0001), coronary heart disease (p < 0.0001), diabetes (p < 0.0001), medication (p = 0.0018), claudication (p < 0.0001), smoking history (p = 0.0001) and chronic obstructive pulmonary disorder (p = 0.0007). AAA is associated with classical vascular risk factors, in addition to other less-well-documented risk factors including previous vascular surgery. These findings have practical implications with the potential to improve future clinical screening of patients in order to reduce AAA mortality.
Topics: Humans; Aortic Aneurysm, Abdominal; Male; Female; Aged; Risk Factors; Middle Aged; Prospective Studies; Longitudinal Studies; Aged, 80 and over; Wales
PubMed: 38946069
DOI: 10.14814/phy2.16130