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Journal of Vascular Surgery Sep 2021The current guidelines recommend elective abdominal aortic aneurysm (AAA) repair at 5.5 cm for men and 5.0 cm for women. However, rupture can occur in patients with an... (Comparative Study)
Comparative Study
OBJECTIVE
The current guidelines recommend elective abdominal aortic aneurysm (AAA) repair at 5.5 cm for men and 5.0 cm for women. However, rupture can occur in patients with an aneurysm smaller than these size thresholds. In the present study, we investigated the proportion of AAAs that rupture at sizes less than elective operative thresholds and compared the outcomes of repair with those of aneurysms that had ruptured at a larger size. Our hypothesis was that the rupture of small AAAs carries mortality similar to that of rupture at larger sizes.
METHODS
The American College of Surgeons National Surgical Quality Improvement Program targeted vascular files for open AAA repair and endovascular aneurysm repair (EVAR) were reviewed for all cases of ruptured AAAs (rAAAs) from 2011 to 2018. The patients were divided into two groups: those with small AAAs that had ruptured at a size less than the current size guidelines for elective repair and those with large AAAs that had ruptured at a size that had met the criteria for elective repair. Univariate analyses were conducted to compare the comorbidities and perioperative outcomes of infrarenal rAAA repair between the groups. Multivariable logistic regression was performed to examine the differences in mortality between small and large rAAAs after controlling for confounding variables.
RESULTS
Of the 1612 rAAA repairs, 167 (10.4%) were small rAAAs. The proportion of small rAAAs did not significantly change during the study period (P = .15). The large rAAA group was more likely to have juxtarenal or suprarenal aneurysms compared with the small rAAA group (27% vs 16%; P = .001). A comparison of infrarenal rAAAs only demonstrated that the mean small rAAA (n = 141) diameter was 4.1 cm in the women and 4.5 cm in the men compared with the large rAAAs (n = 1051), with a mean diameter of 7.1 cm in women and 8.3 cm in men (P < .01 for the women; P < .01 for the men). The patients in the small rAAA group had had a significantly lower body mass index but were more likely to be African American and to have hypertension. The small rAAA group was more likely to present without hypotension and to have undergone EVAR. The repair of small rAAAs was associated with lower bleeding and mortality and a shorter mean operative time but with more readmissions. Multivariable regression analysis demonstrated that size was not associated with outcome after adjusting for other variables.
CONCLUSIONS
Of all AAA repairs classified as treating rupture, 10% were for patients with small AAAs. Patients with small rAAA were less likely to present with hypotension and were more likely to have undergone EVAR. Further research into sac morphology and more sensitive imaging modalities might help identify small rAAAs at high risk of rupture that would benefit from elective repair.
Topics: Aged; Aged, 80 and over; Aortic Aneurysm, Abdominal; Aortic Rupture; Blood Vessel Prosthesis Implantation; Clinical Decision-Making; Databases, Factual; Endovascular Procedures; Female; Humans; Male; Middle Aged; Retrospective Studies; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; United States
PubMed: 33617982
DOI: 10.1016/j.jvs.2021.01.063 -
PLoS Genetics Mar 2022Vascular Ehlers-Danlos syndrome is a rare inherited disorder caused by genetic variants in type III collagen. Its prognosis is especially hampered by unpredictable... (Comparative Study)
Comparative Study
Vascular Ehlers-Danlos syndrome is a rare inherited disorder caused by genetic variants in type III collagen. Its prognosis is especially hampered by unpredictable arterial ruptures and there is no therapeutic consensus. We created a knock-in Col3a1+/G182R mouse model and performed a complete genetic, molecular and biochemical characterization. Several therapeutic strategies were also tested. Col3a1+/G182R mice showed a spontaneous mortality caused by thoracic aortic rupture that recapitulates the vascular Ehlers-Danlos syndrome with a lower survival rate in males, thin non-inflammatory arteries and an altered arterial collagen. Transcriptomic analysis of aortas showed upregulation of genes related to inflammation and cell stress response. Compared to water, survival rate of Col3a1+/G182R mice was not affected by beta-blockers (propranolol or celiprolol). Two other vasodilating anti-hypertensive agents (hydralazine, amlodipine) gave opposite results on aortic rupture and mortality rate. There was a spectacular beneficial effect of losartan, reversed by the cessation of its administration, and a marked deleterious effect of exogenous angiotensin II. These results suggest that blockade of the renin angiotensin system should be tested as a first-line medical therapy in patients with vascular Ehlers-Danlos syndrome.
Topics: Animals; Aortic Rupture; Arteries; Collagen Type III; Disease Models, Animal; Ehlers-Danlos Syndrome; Humans; Male; Mice
PubMed: 35245290
DOI: 10.1371/journal.pgen.1010059 -
Journal of Vascular Surgery Oct 2022Emergent endovascular repair of suprarenal (SRAAAs) and thoracoabdominal aortic aneurysms (TAAAs) poses a significant challenge due to the need for branch vessel...
Comparative early results of in situ fenestrated endovascular aortic repair and other emergent complex endovascular aortic repair techniques for ruptured suprarenal and thoracoabdominal aortic aneurysms at a regional aortic center.
INTRODUCTION
Emergent endovascular repair of suprarenal (SRAAAs) and thoracoabdominal aortic aneurysms (TAAAs) poses a significant challenge due to the need for branch vessel incorporation, time constraints, and lack of dedicated devices. Techniques to incorporate branch vessels have included parallel grafting, physician-modified endografts, double-barrel/reversed iliac branch device, and in situ fenestration (ISF). This study describes a single-center experience and the associated outcomes when using these techniques for ruptured SRAAAs and TAAAs.
METHODS
A retrospective review of patients who underwent endovascular repair of ruptured SRAAAs and TAAAs from July 2014 to March 2021 with branch vessel incorporation was performed. Clinical presentation, intraoperative details, and postoperative outcomes of those who underwent ISF were compared with those who underwent repair using non-ISF techniques. The primary outcome of interest was in-hospital mortality. Secondary outcomes were major adverse events including myocardial infarction, respiratory failure, renal dysfunction, new onset dialysis, bowel ischemia, stroke, and spinal cord ischemia.
RESULTS
Forty-two patients underwent endovascular repair for ruptured SRAAAs and TAAAs, 18 of whom underwent ISF repair. Seventy-two percent of ISF patients were hypotensive before surgery, compared with 46% of the patients who underwent repair using non-ISF techniques (physician-modified endografts, parallel grafting, or double-barrel/reversed iliac branch device). The total procedural and fluoroscopy times were similar between the two groups despite a greater mean number of branch vessels incorporated with the ISF technique (3.1 vs 2.2 per patient, P = .015). In-hospital mortality was 19% for all ruptures and 25% for ruptures with hypotension. Compared with the non-ISF group, in-hospital mortality trended lower in the ISF group (11% vs 25%, P = .233), reaching statistical significance when comparing patients who presented with hypotension (8% vs 45%, P = .048). The rate of major adverse events was 57% across all techniques and did not significantly differ between the ISF and non-ISF groups, with postoperative renal dysfunction being the most frequent complication (48%). Overall, ISF became the most commonly used technique later in the study period.
CONCLUSIONS
Although emergent endovascular repair of ruptured SRAAAs/TAAAs remains a challenge, a number of techniques are available for expeditious treatment. In this series, ISF was associated improve survival, including a fivefold reduction in mortality in patients presenting with hypotension, and has now become the dominant technique at our center. Despite these advantages, postoperative complications and reinterventions are common. Further experience and longer-term follow-up are needed to validate these initial results and assess durability.
Topics: Aortic Aneurysm, Thoracic; Aortic Rupture; Blood Vessel Prosthesis; Blood Vessel Prosthesis Implantation; Endovascular Procedures; Humans; Hypotension; Kidney Diseases; Postoperative Complications; Prosthesis Design; Risk Factors; Time Factors; Treatment Outcome
PubMed: 35697311
DOI: 10.1016/j.jvs.2022.04.036 -
Circulation Journal : Official Journal... Nov 2021Although the high-attenuating crescent (HAC) sign can indicate aortic aneurysm (AA) impending rupture, the relation of its computed tomography (CT) value to the...
BACKGROUND
Although the high-attenuating crescent (HAC) sign can indicate aortic aneurysm (AA) impending rupture, the relation of its computed tomography (CT) value to the aneurysmal status remains unclear. This study compared the HAC sign CT-attenuation values among rupture, impending rupture, and non-rupture AA cases.Methods and Results:This included 76 patients (mean age: 77.0 years) diagnosed with HAC sign-associated AA between January 2005 and July 2015. The CT-attenuation values of the HAC sign (H) and aortic lumen (A) using region-of-interest methodology were measured and the H/A ratio was calculated. The study classified patients into the rupture group (R-G, n=36), impending rupture group (IR-G, n=16), and non-rupture group (NR-G, n=24); the H and the H/A ratio were compared among them. Additionally, the H and the H/A ratio cut-offs between the IR-G and NR-G groups were evaluated. The H and the H/A ratio were significantly higher in the R-G and IR-G than in the NR-G (both P<0.001); the H/A ratio was significantly higher in the R-G than in the IR-G (P=0.038). The optimal cut-off for H between the IR-G and NR-G was 50.3 Hounsfield units (area under the curve [AUC]=0.875; sensitivity=87.5%; specificity=87.5%), and that for the H/A ratio was 1.3 (AUC=0.909; sensitivity=91.7%; specificity=87.5%).
CONCLUSIONS
Among patients with AA, the H and the H/A ratio were significantly higher in cases of rupture and impending rupture than in those of non-rupture.
Topics: Aged; Aorta; Aortic Aneurysm, Abdominal; Aortic Rupture; Area Under Curve; Humans; Tomography, X-Ray Computed
PubMed: 34707030
DOI: 10.1253/circj.CJ-21-0541 -
Journal of Vascular Surgery Nov 2014Rupture after abdominal endovascular aortic aneurysm repair (EVAR) is a function of graft maintenance of the seal and fixation. We describe our 10-year experience with...
OBJECTIVE
Rupture after abdominal endovascular aortic aneurysm repair (EVAR) is a function of graft maintenance of the seal and fixation. We describe our 10-year experience with rupture after EVAR.
METHODS
From 2000 to 2010, 1736 patients with abdominal aortic aneurysm (AAA) from 17 medical centers underwent EVAR in a large, regional integrated health care system. Preoperative demographic and clinical data of interest were collected and stored in our registry. We retrospectively identified patients with postoperative rupture, characterized as "early" and "delayed" rupture (≤30 days and >30 days after the initial EVAR, respectively), and identified predictors associated with delayed rupture.
RESULTS
The overall follow-up rate was 92%, and the median follow-up was 2.7 years (interquartile range, 1.2-4.4 years) in these 1736 EVAR patients. We identified 20 patients with ruptures; 70% were male, the mean age was 79 years, and mean AAA size at the initial EVAR was 6.3 cm. Six patients underwent initial EVAR for rupture (n = 2) or symptomatic presentation (n = 4). Of the 20 post-EVAR ruptures, 25% (five of 20) were early, all occurring within 2 days after the initial EVAR. Of these five patients, four had intraoperative adverse events leading directly to rupture, with one type I and one type III endoleak. Of the five early ruptures, four patients underwent endovascular repair and one received repair with open surgery, resulting in two perioperative deaths. Among the remaining 15 patients, the median time from initial EVAR to rupture was 31.1 months (interquartile range, 13.8-57.3 months). Most of these delayed ruptures (10 of 15) were preceded by AAA sac increases, including three patients with known endoleaks who underwent reintervention. At the time of delayed rupture, nine of 15 patients had new endoleaks. Among all 20 patients, six patients did not undergo repair (all delayed patients) and died, nine underwent repeated EVAR, and five had open repair. For patients who underwent repair for delayed rupture, mortality at 30 days and 1 year were 44.4% and 66.7%, respectively. Multivariable Cox regression analysis identified age 80 to 89 (hazard ratio, 3.3; 95% confidence interval, 1.1-9.4; P = .03), and symptomatic or ruptured initial indication for EVAR (hazard ratio, 7.4; 95% confidence interval, 2.2-24.8; P < .01) as significant predictors of delayed rupture.
CONCLUSIONS
Rupture after EVAR is a rare but devastating event, and mortality after repair exceeds 60% at 1 year. Most delayed cases showed late AAA expansion, thereby implicating late loss of seal and increased endoleaks as the cause of rupture in these patients and mandating vigilant surveillance.
Topics: Aged; Aged, 80 and over; Aortic Aneurysm, Abdominal; Aortic Rupture; Blood Vessel Prosthesis Implantation; Chi-Square Distribution; Endoleak; Endovascular Procedures; Female; Humans; Male; Multivariate Analysis; Proportional Hazards Models; Registries; Reoperation; Retrospective Studies; Risk Factors; Time Factors; Treatment Outcome; United States
PubMed: 24957409
DOI: 10.1016/j.jvs.2014.05.046 -
Journal of Vascular Surgery Feb 2018The objective of this study was to summarize the literature regarding the effects of renin-angiotensin system blockade (RASB) using angiotensin-converting enzyme... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The objective of this study was to summarize the literature regarding the effects of renin-angiotensin system blockade (RASB) using angiotensin-converting enzyme inhibitors (ACEis) or angiotensin receptor blockers (ARBs) on human abdominal aortic aneurysm (AAA) growth, rupture, and perioperative mortality.
METHODS
We conducted a systematic review in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Our review protocol was registered at the International Prospective Register of Systematic Reviews (CRD42016054082). We searched the Cochrane Central Register of Controlled Trials database, MEDLINE, and Embase from inception to 2017 for studies examining the effects of ACEi or ARB treatment on AAA growth, rupture, or perioperative mortality. Review, abstraction, and quality assessment were conducted in duplicate, and a third author resolved discrepancies. We assessed study quality using the Cochrane and Newcastle-Ottawa scales. We used random-effects models to calculate pooled mean differences and odds ratios (ORs) with 95% confidence intervals (CIs). Heterogeneity was quantified using the I statistic.
RESULTS
Our search yielded 525 articles. One randomized and seven observational studies involving 35,448 patients were included. Inter-rater agreement was excellent (κ = 0.78), and risk of bias was low to moderate. All studies investigated ACEis, three studies investigated ARBs, and two studies included a composite RASB group consisting of ACEi or ARB users. Five studies assessed AAA growth, two assessed rupture rate, and one reported 30-day mortality after elective open repair. There was no difference in AAA growth rate between RASB and control (mean difference, 0.03 mm/y; 95% CI, -0.40 to 0.46; P = .88; I = 60%). No protective effect of RASB (OR, 0.92; 95% CI, 0.72, 1.16; P = .47; I = 90%) was demonstrated for AAA rupture. Finally, RASB increased 30-day mortality in patients undergoing elective open AAA repair (OR, 5; 95% CI, 1.4, 27) according to a single well-adjusted study.
CONCLUSIONS
RASB does not appear to affect AAA growth and rupture rate but increases elective perioperative mortality. The small number of heterogeneous, retrospective studies and limited long-term follow-up preclude a definitive dismissal of RASB as pharmacotherapy for AAA. Prospective, long-term data are needed to clarify the effect of RASB on AAA growth, rupture, and perioperative mortality.
Topics: Aged; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Aortic Aneurysm, Abdominal; Aortic Rupture; Blood Vessel Prosthesis Implantation; Chi-Square Distribution; Elective Surgical Procedures; Endovascular Procedures; Female; Humans; Male; Odds Ratio; Renin-Angiotensin System; Risk Factors; Treatment Outcome
PubMed: 29175038
DOI: 10.1016/j.jvs.2017.09.007 -
The Journal of Thoracic and... May 2019The risk of rupture and dissection in ascending thoracic aortic aneurysms increases as the aortic diameter exceeds 5 cm. This study evaluates the clinical effectiveness...
OBJECTIVE
The risk of rupture and dissection in ascending thoracic aortic aneurysms increases as the aortic diameter exceeds 5 cm. This study evaluates the clinical effectiveness of a specific algorithm based on size and symptoms for preemptive surgery to prevent complications.
METHODS
A total of 781 patients with nondissecting ascending thoracic aortic aneurysms who presented electively for evaluation to our institution from 2011 to 2017 were triaged to surgery (n = 607, 77%) or medical observation (n = 181, 24%) based on a specific algorithm: surgery for large (>5 cm) or symptomatic aneurysms. A total of 309 of 781 patients did not undergo surgery. Of these, 128 (16%) had been triaged to prompt repair but did not undergo surgery for a variety of reasons ("surgery noncompliant and overwhelming comorbidities" group). Another 181 patients (24%) were triaged to medical management ("medical" group).
RESULTS
In the "surgery noncompliant and overwhelming comorbidities" versus the "medical" group, mean aortic diameters were 5 ± 0.5 cm versus 4.45 ± 0.4 cm and aortic events (rupture/dissection) occurred in 17 patients (13.3%) versus 3 patients (1.7%), respectively (P < .001). Later elective surgeries (representing late compliance in the "surgery noncompliant and overwhelming comorbidities group" or onset of growth or symptoms in the "medical" group) were conducted in 21 patients (16.4%) versus 15 patients (8.3%) (P = .04), respectively. Death ensued in 20 patients (15.6%) versus 6 patients (3.3%) (P < .001), respectively. In the "surgery noncompliant and overwhelming comorbidities" group, 7 of 20 patients died of definite aortic causes compared with none in the "medical" group.
CONCLUSIONS
Patients with ascending thoracic aortic aneurysms who did not follow surgical recommendations experienced substantially worse outcomes compared with medically triaged candidates. The specific algorithm based on size and symptoms functioned effectively in the clinical setting, correctly identifying both at-risk and safe patients.
Topics: Aged; Aged, 80 and over; Algorithms; Aortic Dissection; Aortic Aneurysm, Thoracic; Aortic Rupture; Clinical Decision-Making; Comorbidity; Databases, Factual; Decision Support Techniques; Disease Progression; Female; Humans; Male; Middle Aged; Patient Compliance; Patient Selection; Predictive Value of Tests; Retrospective Studies; Risk Assessment; Risk Factors; Treatment Outcome; Triage; Vascular Surgical Procedures
PubMed: 30579535
DOI: 10.1016/j.jtcvs.2018.09.124 -
Annals of Biomedical Engineering Jan 2016Dissection of an artery is characterised by the separation of the layers of the arterial wall causing blood to flow within the wall. The incidence rates of thoracic... (Review)
Review
Dissection of an artery is characterised by the separation of the layers of the arterial wall causing blood to flow within the wall. The incidence rates of thoracic aortic dissection (AoD) are increasing, despite falls in virtually all other manifestations of cardiovascular disease, including abdominal aortic aneurysm (AAA). Dissections involving the ascending aorta (Type A) are a medical emergency and require urgent surgical repair. However, dissections of the descending aorta (Type B) are less lethal and require different clinical management whereby the patient may not be offered surgery unless complicating factors are present. But how do we tell if a patient will develop a complication later on? Currently, there is no consensus and the evidence base is limited. There is an opportunity for computational biomechanics to help clinicians decide as to which cases to repair and which to manage with blood pressure control. In this review article, we look at AoD from both the clinical and biomechanical perspective and discuss some of the recent computational studies of both Type A and B AoD. We then focus more on Type B where the real opportunity for patient-specific modelling exists. Finally, we look ahead at some of the promising areas of research that may help clinicians improve the decision-making process surrounding Type B AoD.
Topics: Animals; Aortic Aneurysm, Abdominal; Aortic Rupture; Computer Simulation; Humans; Models, Cardiovascular
PubMed: 26101036
DOI: 10.1007/s10439-015-1366-8 -
Journal of Vascular Surgery Jan 2017The purpose of this study was to compare findings at presentation and surgical outcomes in patients in whom abdominal aortic aneurysms (AAAs) ruptured after endovascular... (Comparative Study)
Comparative Study
OBJECTIVE
The purpose of this study was to compare findings at presentation and surgical outcomes in patients in whom abdominal aortic aneurysms (AAAs) ruptured after endovascular repair and in patients in whom AAAs ruptured before any treatment during a defined period at a single center.
METHODS
This is a retrospective analysis of consecutive patients who presented to Royal Prince Alfred Hospital with ruptured AAA from September 2003 to September 2014. Medical records of each patient were reviewed to retrieve demographics, findings at presentation, and surgical outcome. Comparison of the outcomes between those occurring after endovascular repair (group 1) and those occurring without previous endovascular treatment (group 2) was made using the data collected and combining the results obtained by a previous study that analyzed the same findings between 1992 and 2003 from the same center to provide a total 22-year experience (1992-2014) at a single quaternary referral center.
RESULTS
From May 1992 to September 2014, there were 1921 elective repairs of intact infrarenal AAAs, with 1288 endovascular and 633 open repairs. During 22 years, 40 of the 1288 patients (3.1%) who underwent endovascular repair for AAA had rupture. The proportion of patients with hypotension at presentation in group 1 (13/40) was significantly less than in group 2 (108/138; P < .01). The difference in perioperative 30-day mortality rate in group 1 (8/40 [20%]) compared with group 2 (68/138 [49%]) was significant (P < .01).
CONCLUSIONS
This study confirmed that endovascular AAA repair does not prevent rupture in all patients. The data suggest that rupture, when it does occur, may not be accompanied by such major hemodynamic changes and higher mortality rate as with rupture of an untreated AAA. Strict surveillance and follow-up are required, especially in patients with relatively large initial AAA diameter or presence of endoleak and graft migration, to reduce the rate of ruptures after endovascular repair. Complete prevention will remain challenging because rupture may occur without any predisposing abnormalities. With the advent of new-generation devices, continuous larger long-term studies are required to document reduction in rupture rates after endovascular aneurysm repair.
Topics: Aged; Aortic Aneurysm, Abdominal; Aortic Rupture; Blood Vessel Prosthesis; Blood Vessel Prosthesis Implantation; Endovascular Procedures; Female; Humans; Male; New South Wales; Prosthesis Design; Retrospective Studies; Risk Factors; Time Factors; Treatment Outcome
PubMed: 27575810
DOI: 10.1016/j.jvs.2016.05.090 -
American Journal of Physiology. Heart... May 2021Thoracic aortic aneurysm and dissection (TAAD) is a deadly disease characterized by intimal disruption induced by hemodynamic forces of the circulation. The effect of...
Thoracic aortic aneurysm and dissection (TAAD) is a deadly disease characterized by intimal disruption induced by hemodynamic forces of the circulation. The effect of exercise in patients with TAAD is largely unknown. β-Aminopropionitrile (BAPN) is an irreversible inhibitor of lysyl oxidase that induces TAAD in mice. The objective of this study was to investigate the effect of aerobic exercise on BAPN-induced TAAD. Upon weaning, mice were given either BAPN-containing water or standard drinking water and subjected to either conventional cage activity (BAPN-CONV) or forced treadmill exercise (BAPN-EX) for up to 26 wk. Mortality was 23.5% (20/85) for BAPN-CONV mice versus 0% (0/22) for BAPN-EX mice (hazard ratio 3.8; = 0.01). BAPN induced significant elastic lamina fragmentation and intimal-medial thickening compared with BAPN-untreated controls, and aneurysms were identified in 50% (5/10) of mice that underwent contrast-enhanced CT scanning. Exercise significantly decreased BAPN-induced wall thickening, calculated circumferential wall tension, and lumen diameter, with 0% (0/5) of BAPN-EX demonstrating chronic aortic aneurysm formation on CT scan. Expression of selected genes relevant to vascular diseases was analyzed by qRT-PCR. Notably, exercise normalized BAPN-induced increases in TGF-β pathway-related genes , , and ; inflammation-related genes , , , , , , , and ; and vascular injury- and response-related genes , , and . Additionally, exercise significantly increased elastin expression in BAPN-treated animals compared with controls. This study suggests that moderate aerobic exercise may be safe and effective in preventing the most devastating outcomes in TAAD. Moderate aerobic exercise was shown to significantly reduce mortality, extracellular matrix degradation, and thoracic aortic aneurysm and dissection formation associated with lysyl oxidase inhibition in a mouse model. Gene expression suggested a reversal of TGF-β, inflammation, and extracellular matrix remodeling pathway dysregulation, along with augmented elastogenesis with exercise.
Topics: Aminopropionitrile; Aortic Dissection; Animals; Aorta, Thoracic; Aortic Aneurysm, Thoracic; Aortic Rupture; Dilatation, Pathologic; Disease Models, Animal; Disease Progression; Exercise Therapy; Extracellular Matrix; Extracellular Matrix Proteins; Gene Expression Regulation; Hemodynamics; Male; Mice, Inbred C57BL; Proteolysis; Signal Transduction; Vascular Remodeling; Mice
PubMed: 33635167
DOI: 10.1152/ajpheart.00229.2020