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Hypertension (Dallas, Tex. : 1979) Dec 2023Cardiac hypertrophy and subsequent heart failure impose a considerable burden on public health worldwide. Impaired protein degradation, especially endo-lysosome-mediated...
BACKGROUND
Cardiac hypertrophy and subsequent heart failure impose a considerable burden on public health worldwide. Impaired protein degradation, especially endo-lysosome-mediated degradation of membrane proteins, is associated with cardiac hypertrophy progression. CHMP4C (charged multivesicular body protein 4C), a critical constituent of multivesicular bodies, is involved in cellular trafficking and signaling. However, the specific role of CHMP4C in the progression of cardiac hypertrophy remains largely unknown.
METHODS
Mouse models with CHMP4C knockout or cardiadc-specific overexpression were subjected to transverse aortic constriction surgery for 4 weeks. Cardiac morphology and function were assessed through histological staining and echocardiography. Confocal imaging and coimmunoprecipitation assays were performed to identify the direct target of CHMP4C. An EGFR (epidermal growth factor receptor) inhibitor was administrated to determine whether effects of CHMP4C on cardiac hypertrophy were EGFR dependent.
RESULTS
CHMP4C was significantly upregulated in both pressure-overloaded mice and spontaneously hypertensive rats. Compared with wild-type mice, CHMP4C deficiency exacerbated transverse aortic constriction-induced cardiac hypertrophy, whereas CHMP4C overexpression in cardiomyocytes attenuated cardiac dysfunction. Mechanistically, the effect of CHMP4C on cardiac hypertrophy relied on the EGFR signaling pathway. Fluorescent staining and coimmunoprecipitation assays confirmed that CHMP4C interacts directly with EGFR and promotes lysosome-mediated degradation of activated EGFR, thus attenuating cardiac hypertrophy. Notably, an EGFR inhibitor canertinib counteracted the exacerbation of cardiac hypertrophy induced by CHMP4C knockdown in vitro and in vivo.
CONCLUSIONS
CHMP4C represses cardiac hypertrophy by modulating lysosomal degradation of EGFR and is a potential therapeutic candidate for cardiac hypertrophy.
Topics: Rats; Mice; Animals; Endosomal Sorting Complexes Required for Transport; Cardiomegaly; Heart Failure; ErbB Receptors; Myocytes, Cardiac; Lysosomes; Mice, Knockout; Mice, Inbred C57BL; Disease Models, Animal
PubMed: 37846580
DOI: 10.1161/HYPERTENSIONAHA.123.21427 -
Annals of Surgical Oncology Aug 2017The purpose of this retrospective study was to evaluate the incidence and prognostic value of metastases to "posterior" (8p, 12b/p, 13) and para-aortic lymph nodes in a...
BACKGROUND
The purpose of this retrospective study was to evaluate the incidence and prognostic value of metastases to "posterior" (8p, 12b/p, 13) and para-aortic lymph nodes in a large cohort of Western patients submitted to D2 plus lymphadenectomy.
METHODS
Removal of "posterior" nodes was performed in 743 patients, and para-aortic lymphadenectomy in a subgroup of 390 patients. After lymph node mapping and retrieval on the fresh specimen, a median number of 41 total lymph nodes were analyzed. The median follow-up period was 37 months for the entire series and 68 months for survivors.
RESULTS
Of 743 included patients, 23 (3.1%) had metastases in station 8p, 12 (1.6%) in station 12b/p, and 19 (2.6%) in station 13. On the whole, 47 of 743 patients (6.3%) had positive "posterior" nodes. Para-aortic metastases were present in 42 of 390 patients (10.8%). Metastases to "posterior" stations were significantly related to depth of invasion, number of positive nodes, and surgical radicality. Distal tumors showed higher trend to metastasize to "posterior" nodes than upper third, whereas for para-aortic metastases it was the reverse. 5-year survival in patients with positivity to "posterior" nodes was 17%, with no significant difference according to 8p, 12b/p, and 13 stations; long-term outcome was overlapping to pN3b stage. 5-year survival in para-aortic positive cases was 11%, and a trend to better outcome was observed in proximal tumors.
CONCLUSIONS
Although metastases to "posterior" and para-aortic nodes are expression of an advanced nodal stage, not negligible survival rates are observed in subgroups of patients.
Topics: Adult; Aged; Aged, 80 and over; Female; Follow-Up Studies; Humans; Incidence; Italy; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Para-Aortic Bodies; Postoperative Complications; Prognosis; Retrospective Studies; Stomach Neoplasms; Survival Rate; Young Adult
PubMed: 28405772
DOI: 10.1245/s10434-017-5857-8 -
Bulletin of Experimental Biology and... Jan 2021Using postmortem MRI, we studied the features of the development of internal cadaveric hypostasis in dead newborns. Postmortem radiological and pathoanatomical...
Using postmortem MRI, we studied the features of the development of internal cadaveric hypostasis in dead newborns. Postmortem radiological and pathoanatomical examination of 62 bodies of newborns and infants who died at the age of 1.5 h to 49 days was carried out. After the death was ascertained, prior to MRI, the bodies were stored in a refrigerator at 4°C in the supine position. Depending on the duration of the postmortem period (2-72 h), all observations were divided into eight groups. Prior to autopsy, an MRI scan was performed in T1 and T2 standard modes, followed by analysis of the presence and severity of the gradient line of the intensity of the MR signal in the liver and lung tissue in the ventral (overlying) and dorsal (underlying) areas, as well as the presence of a gradient of the intensity of the blood signal in the heart cavity and in the aortic lumen. The main manifestations of cadaveric hypostasis in the liver and lungs are changes of the MR signal intensity in the ventral and dorsal regions with the appearance of a horizontal gradient of the MR signal intensity, which reflects the location of the body after death. In the heart cavity and in the aortic lumen, there is also a gradient of the blood signal intensity of various severity with the visualization of two or three of its layers. The revealed features of the MRI signal intensity and, accordingly, the presence of its horizontal gradient depended not only on the MRI mode of the study, but also on the studied organ and the duration of the postmortem period. This should be taken into account when analyzing the results of virtopsy and determining the links of thanatogenesis of dead newborns and infants.
Topics: Autopsy; Cadaver; Diagnosis; Humans; Infant, Newborn; Liver; Lung; Magnetic Resonance Imaging
PubMed: 33452989
DOI: 10.1007/s10517-021-05070-1 -
JACC. Cardiovascular Imaging May 2018
Topics: Aortic Valve; Aortic Valve Stenosis; Humans; Prognosis; Registries; Transcatheter Aortic Valve Replacement
PubMed: 28528152
DOI: 10.1016/j.jcmg.2017.01.026 -
Vascular and Endovascular Surgery Oct 2020The attempt to repair a ruptured abdominal aortic aneurysm carries a significant risk of perioperative mortality. The relationship between body mass index (BMI) and...
OBJECTIVE
The attempt to repair a ruptured abdominal aortic aneurysm carries a significant risk of perioperative mortality. The relationship between body mass index (BMI) and outcomes after repair of ruptured abdominal aortic aneurysms (AAAs) has not been well defined. We report the association of BMI with outcomes after ruptured AAA repair.
METHODS
Patients undergoing ruptured AAA repairs between 2008 and 2017 at 2 tertiary academic centers were included in this retrospective study. Demographics (including BMI), type of repair, length of stay, and admission mortality risk scores were gathered and analyzed using bivariate and multivariate logistic regressions. Adjusted odds ratio (AOR) was reported with 95% CIs and values from the multivariate analysis. The primary outcome was 30-day mortality. Akaike information criterion (AIC) and c-statistics were used to assess the predictive power of models including physiologic score with or without BMI.
RESULTS
A total of 202 patients underwent repair of ruptured AAA. In bivariate relationship, increased BMI was significantly associated with 30-day mortality. With multivariate analysis, adjusting for demographics, type of procedure, and physiologic score, for each kg/m increase in BMI, an 8% increase in the likelihood of perioperative mortality (AOR = 1.08, 95% CI: 1.01-1.17; = .04) was observed.
CONCLUSION
When adjusted for admission risk score, type of procedure, and demographics, obesity was associated with increased 30-day mortality. With BMI as an additional data point, the c-statistics and AIC comparisons indicated that we would have a greater ability to preoperatively estimate mortality after ruptured AAA repair. Consideration could be made to include BMI in future mortality risk scoring systems for ruptured AAA.
Topics: Aged; Aged, 80 and over; Aortic Aneurysm, Abdominal; Aortic Rupture; Body Mass Index; Female; Humans; Indiana; Male; Middle Aged; Obesity; Retrospective Studies; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Vascular Surgical Procedures; Washington
PubMed: 32643559
DOI: 10.1177/1538574420939356 -
BioRxiv : the Preprint Server For... Feb 2023Abdominal aortic aneurysms (AAAs) are common in aging populations, and AAA rupture is associated with high morbidity and mortality. There is currently no effective...
Abdominal aortic aneurysms (AAAs) are common in aging populations, and AAA rupture is associated with high morbidity and mortality. There is currently no effective medical preventative therapy for AAAs to avoid rupture. It is known that the monocyte chemoattractant protein (MCP-1) / C-C chemokine receptor type 2 (CCR2) axis critically regulates AAA tissue inflammation, matrix-metalloproteinase (MMP) production, and in turn extracellular matrix (ECM) stability. However, therapeutic modulation of the CCR2 axis for AAA disease has so far not been accomplished. Since ketone bodies (KBs) are known to trigger repair mechanisms in response to vascular tissue inflammation, we evaluated whether systemic ketosis can impact CCR2 signaling, and therefore impact AAA expansion and rupture. To evaluate this, male Sprague-Dawley rats underwent surgical AAA formation using porcine pancreatic elastase (PPE), and received daily β-aminopropionitrile (BAPN) to promote AAA rupture. Animals with formed AAAs received either a standard diet (SD), ketogenic diet (KD), or exogenous KB supplements (EKB). Animals that received KD and EKB reached a state of ketosis, and had significantly reduced AAA expansion and incidence of rupture. Ketosis also led to significantly reduced CCR2, inflammatory cytokine content, and infiltrating macrophages in AAA tissue. Additionally, animals in ketosis had improved balance in aortic wall matrix-metalloproteinase (MMP), reduced extracellular matrix (ECM) degradation, and higher aortic media Collagen content. This study demonstrates that ketosis plays an important therapeutic role in AAA pathobiology, and provides the impetus for future studies investigating the role of ketosis as a preventative strategy for individuals with AAAs.
PubMed: 36865192
DOI: 10.1101/2023.02.21.529460 -
Nigerian Journal of Clinical Practice Mar 2020The abdominal aorta is the largest artery in the human body. Sonographic assessment of the abdominal aortic diameter is presently the preferred screening method for an...
BACKGROUND
The abdominal aorta is the largest artery in the human body. Sonographic assessment of the abdominal aortic diameter is presently the preferred screening method for an aortic aneurysm. However, there are no customized nomograms for our population and the recommended cutoffs for screening may be inappropriate. The effect of factors such as age, gender, and body mass index (BMI) on the abdominal aortic dissection (AAD) among blacks has also not been extensively investigated.
OBJECTIVE
To develop a nomogram of AAD at various levels in Nigerian adults using high-resolution B mode ultrasonography and to evaluate the effect of factors such as gender, age, and BMI on AAD.
METHODOLOGY
This study involved a sonographic evaluation of the abdominal aortic diameter of 400 normal Nigerian adults aged 18 years and above over a period of 17 months. The scan was done using a 3.5-5 MHz curvilinear transducer on the Mindray ultrasound machine (model: DC-8, SN-QE3B001806). The AAD (mean ± SD) was correlated with age, gender, BMI, and body surface area (BSA). Data were analyzed using SPSS version 20 for windows and P values <0.05 were considered significant.
RESULTS
The mean AADs decreased from 1.58 ± 0.24 cm in the upper aorta (D1) to 1.40 ± 0.20 cm at the level of the renal arteries (D2) and 1.29 ± 0.23 cm at the bifurcation (D3). Mean AAD was significantly higher at all levels of the abdominal aorta (D1, D2, and D3) in males than in females (P < 0.00) and correlated positively with age (P = 0.00) and height (P = 0.00) at D2 and D3 levels.
CONCLUSION
Absolute AADs were relatively smaller in adult Nigerians and this should be considered when setting up screening programs for abdominal aortic aneurysm in our population. Further studies are needed to determine factors affecting AAD.
Topics: Adolescent; Adult; Aged; Aorta, Abdominal; Aortic Aneurysm, Abdominal; Body Mass Index; Body Surface Area; Cross-Sectional Studies; Female; Humans; Male; Middle Aged; Nigeria; Reference Values; Renal Artery; Ultrasonography; Young Adult
PubMed: 32134028
DOI: 10.4103/njcp.njcp_33_19 -
Journal of the American College of... Jan 2020Causal risk factors for aortic valve stenosis are poorly understood, limiting the possibility of preventing the most common heart valve disease. (Observational Study)
Observational Study
BACKGROUND
Causal risk factors for aortic valve stenosis are poorly understood, limiting the possibility of preventing the most common heart valve disease.
OBJECTIVES
The hypothesis was tested that genetically based obesity measured by body mass index is causally associated with risk of aortic valve stenosis and replacement.
METHODS
The authors included 108,211 individuals from the Copenhagen General Population Study. Participants had measurements of body mass index, waist-hip ratio, and waist circumference, and information on 5 genetic variants associated with obesity. A Mendelian randomization design was used to investigate genetic and observational associations of obesity with incident aortic valve stenosis (n = 1,215) and replacement (n = 467) for a median follow-up time of 8.7 years.
RESULTS
Genetically increased body mass index was causally associated with increased risk of aortic valve stenosis. Compared with an unweighted allele score of 0 to 3, individuals with an allele score 7 to 10 had a mean increase in body mass index of 0.87 kg/m, and the age and sex-adjusted hazard ratio for aortic valve stenosis was 1.3 (95% confidence interval [CI]: 1.0 to 1.7) for allele score 4, 1.4 (95% CI: 1.1 to 1.8) for allele score 5 to 6, and 1.6 (95% CI: 1.3 to 2.1) for allele score 7 to 10 (p for trend: 9 × 10). A 1-kg/m increase in body mass index was associated with causal risk ratios for aortic valve stenosis and replacement, respectively, of 1.52 (95% CI: 1.23 to 1.87) and 1.49 (95% CI: 1.07 to 2.08) genetically, and with corresponding hazard ratios of 1.06 (95% CI: 1.05 to 1.08) and 1.06 (95% CI: 1.03 to 1.08) observationally.
CONCLUSIONS
Obesity from human genetics was causally associated with higher risk of aortic valve stenosis and replacement.
Topics: Aged; Aortic Valve Stenosis; Cohort Studies; Denmark; Female; Follow-Up Studies; Humans; Male; Mendelian Randomization Analysis; Middle Aged; Obesity; Prospective Studies; Risk Factors; Waist-Hip Ratio
PubMed: 31948645
DOI: 10.1016/j.jacc.2019.10.050 -
Journal of Vascular Surgery Nov 2018The aim of this study was to define how the proximal landing zone changes geometrically after endovascular abdominal aortic aneurysm repair (EVAR) with the Anaconda...
OBJECTIVE
The aim of this study was to define how the proximal landing zone changes geometrically after endovascular abdominal aortic aneurysm repair (EVAR) with the Anaconda (Vascutek, Inchinnan, United Kingdom) stent graft.
METHODS
Among 230 patients who underwent Anaconda stent graft implantation between 2005 and 2014, we included 126 with adequate computed tomography (CT) image quality and follow-up. CT analysis entailed the geometric changes in the main body, proximal rings, and proximal landing zone. The median CT follow-up was 2.0 years (345.8 patients-years).
RESULTS
The proximal portion of the main body ring system flattened within the first year after EVAR, resulting in an up to 30° increase in the upper ring's angle in 40% patients and up to 40° increase in 24% patients. One year after EVAR, the upper ring angle increase slowed down. Aortic diameter measured at the level of the upper and lower ring expanded by 2 to 4 mm within 1 year, but remained unchanged afterward. The main body migrated continuously down toward the aortic bifurcation, attaining an average 6-mm increase in the distance between the superior mesenteric artery and main body within 4 years. Freedom from endoleak type IA was 95 ± 2% and 93 ± 3% after 1 and 4 years, respectively.
CONCLUSIONS
The Anaconda main body ring system in its proximal portion flattens within the first year after EVAR, leading to an increase of 2 to 4 mm in the proximal landing zone's aortic diameter. The main body migrates slowly but continuously down toward the aortic bifurcation.
Topics: Aged; Aortic Aneurysm, Abdominal; Aortography; Blood Vessel Prosthesis; Blood Vessel Prosthesis Implantation; Computed Tomography Angiography; Endoleak; Endovascular Procedures; Female; Foreign-Body Migration; Humans; Male; Middle Aged; Prosthesis Design; Prosthesis Failure; Retrospective Studies; Stents; Time Factors; Treatment Outcome
PubMed: 29804739
DOI: 10.1016/j.jvs.2018.02.041 -
General Thoracic and Cardiovascular... Jan 2019In the absence randomized data for assessing the best and optimal temperature for managing open aortic arch surgery patients, cerebral protection method is still... (Review)
Review
In the absence randomized data for assessing the best and optimal temperature for managing open aortic arch surgery patients, cerebral protection method is still performed through hypothermic circulatory arrest with or without the use of adjuncts. A recent consensus has emerged setting to define the temperature levels. In an attempt, this was aimed to establish a solid ground for future trials in aortic arch surgery. This article reviews the current literature and the evidences behind using different temperature methods and their outcomes in patients undergoing open aortic arch surgery.
Topics: Aorta, Thoracic; Aortic Aneurysm, Thoracic; Body Temperature; Brain; Cerebrovascular Circulation; Circulatory Arrest, Deep Hypothermia Induced; Humans; Randomized Controlled Trials as Topic
PubMed: 29147918
DOI: 10.1007/s11748-017-0867-9