Hyperglycemia modulates plasminogen activator inhibitor-1 expression and aortic diameter in experimental aortic aneurysm disease

Dua, Monica M.; Miyama, Noriyuki; Azuma, Junya; Schultz, Geoffrey M.; Sho, Mien; Morser, John; Dalman, Ronald L.

doi:10.1016/j.surg.2010.05.014

Cited by 77 publications

(62 citation statements)

References 25 publications

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“…[27][28][29][30] In addition, ARB and hyperglycemia have inhibited the expansion in animal studies. [31][32][33][34] In the present study, ARB (P=0.025 on univariate analysis) and hyperglycemia (P=0.037 on univariate analysis, P=0.067 on multivariate analysis) tended to be negatively associated with AAA expansion, consistent with previous reports. 31 -34 In addition, we did not observe any suppressive effects on AAA expansion of decreased cholesterol, oral statin use, or lower blood pressure.…”

Section: Other Factorssupporting

confidence: 92%

Oral Steroid Use and Abdominal Aortic Aneurysm Expansion　― Positive Association ―

Tajima

Gotō

Ohara

et al. 2017

Circ J

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such as vascular prosthesis implantation or endovascular aneurysm repair (EVAR); so far, no medical therapy has been established. 7-9 Surgical treatment is highly invasive, and even elective surgery is associated with a 30-day mortality rate of 5.4%. 7 Surgical treatment is therefore indicated only for cases in which the risk of rupture is higher than the operative mortality rate.The maximum axial diameter (MAD) of the aneurysm is an indicator of rupture risk in fusiform AAA; the greater the MAD, the higher the risk of rupture. 7,8,10 In Europe and the USA, comparisons of the rate of rupture and postoperative mortality rate have led to the surgical indication of MAD ≥55 mm; in Japan, the common surgical indication is ≥50 mm, which takes body size into consideration. 7,8,11 For women, the surgical indication is sometimes taken as MAD ≥45 mm because the rupture risk in women has been reported to be 3-fold higher than in men. 11 Patients with smaller AAA (MAD <50 mm), for whom surgery is not A bdominal aortic aneurysm (AAA) is a pathological condition in which the abdominal aorta has a diameter >30 mm, or 1.5-fold greater than normal at the level of the renal artery. 1 Most AAA are asymptomatic, but once rupture occurs, the condition has a mortality rate of 65-85% and is ranked as the 16th most prominent cause of death in the USA in individuals aged ≥65 years. 2,3 In Europe and the USA, the prevalence of the condition is 2% in men aged ≥65 years, with major risk factors for morbidity including male sex, age, history of smoking, and Caucasian race. 3,4 The etiology in the majority of AAA is considered to be atherosclerosis, but a causal relationship with the typical risk factors for atherosclerosis, such as hypertension, dyslipidemia, and diabetes mellitus, remains unclear. 5 Indeed, a negative correlation with diabetes mellitus has been shown, suggesting that AAA is a pathological state distinct from atherothrombosis. 4-6The only treatment option for this condition is surgery, The maximum axial diameter (MAD) of a fusiform abdominal aortic aneurysm (AAA) is an indicator of the risk of expansion or rupture. Apart from smoking and MAD itself, few expansion risk factors have been reported. In this study, we investigated expansion risk factors for AAA.

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Section: Other Factorssupporting

confidence: 92%

Oral Steroid Use and Abdominal Aortic Aneurysm Expansion　― Positive Association ―

Tajima

Gotō

Ohara

et al. 2017

Circ J

Self Cite

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“…The PAI-1 immunostaining was located in the intima and media of the vessel wall. In a rodent model of AAA formation, diabetic mice had decreased aortic diameter, increased plasma PAI-1 levels, and decreased plasmin levels compared with nondiabetic animals undergoing the same procedure (8). Immunostaining confirmed increased intensity of PAI-1 in the diabetic mice, again concentrated in the intima and media of the aorta.…”

Section: Discussionmentioning

confidence: 81%

Increased PAI-1 in females compared with males is protective for abdominal aortic aneurysm formation in a rodent model

DiMusto

Ghosh

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

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The serine proteases, along with their inhibitor plasmin activator inhibitor-1 (PAI-1), have been shown to play a role in abdominal aortic aneurysm (AAA) formation. The aim of this study is to determine if PAI-1 may be a protective factor for AAA formation and partially responsible for the gender difference observed in AAAs. Male and female wild-type (WT) C57BL/6 and PAI-1−/−mice 8–12 wk of age underwent aortic perfusion with porcine pancreatic elastase. Animals were harvested 14 days following perfusion and analyzed for phenotype, PAI-1 protein levels, and matrix metalloproteinase (MMP)-9 and -2 activity. WT males had an average increase in aortic diameter of 80%, whereas females only increased 32% ( P < 0.001). PAI-1−/−males increased 204% and females 161%, significantly more than their WT counterparts ( P < 0.001). Western blot revealed 61% higher PAI-1 protein levels in the WT females compared with the WT males ( P = 0.01). Zymography revealed higher levels of pro-MMP-2 and active MMP-2 in the PAI-1−/−males and females compared with their WT counterparts. PAI-1−/−females had significantly higher serum plasmin levels compared with WT females ( P = 0.003). In conclusion, WT female mice are protected from aneurysm formation and have higher levels of PAI-1 compared with males during experimental aneurysm formation. Additionally, both male and female PAI-1−/−animals develop significantly larger aneurysms than WT animals, correlating with higher pro- and active MMP-2 levels. These findings suggest that PAI-1 is protective for aneurysm formation in the elastase model of AAA and plays a role in the gender differences seen in AAA formation.

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“…By intracoronary ultrasound, researchers found that diabetics with atherosclerosis have less compensatory coronary artery enlargement than non-diabetics and the researchers considered it can explain the diffuse and accelerated course of coronary artery disease in these patients (38). Patients with a longer duration of diabetes who were treated with insulin had (paradoxically) less reference segment and stenosis plaque accumulation and hyperglycemia increases plasminogen activator inhibitor 1 expression and attenuates AAA diameter had been demonstrated by animal experimental studies (39,40), lowering of serum glucose levels with insulin treatment diminishes this protective effect (41). Other researchers argued that diabetes promotes negative arterial wall remodeling or at least impairs compensatory arterial enlargement during the course of the atherosclerotic process (10).…”

Section: Discussionmentioning

confidence: 99%

Relation of diabetes to coronary artery ectasia: A meta-analysis study

Huang¹,

Li²,

Chen³

et al. 2014

Anadolu Kardiyol Derg

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Relation of diabetes to coronary artery ectasia: A meta-analysis study ABSTRACT Objective: Previous studies have shown a significant negative association between diabetes and abdominal aortic aneurysm. However, the relation of diabetes to coronary artery ectasia (CAE) has not well established. The aim of the current study was to conduct a systemic review for evaluating the relationship between diabetes and CAE. Methods: A systemic search of electronic databases (PUBMED, EMBASE, OVID, WEB OF SCIENCE, THE COCHRANCE LIBRARY) from 1970 to March 2013 was performed. Additionally, checking reference lists from identified articles, reviews, and the abstracts presented at related scientific meetings were also carried out. All case-control studies investigating appropriate prevalence data were included. Results: Among 328 articles, 10 case-control studies were finally identified. The prevalence of diabetes in studied patients with CAE was 8% to 33%, while in those without CAE was ranged from 13.5% to 35%. Pooled analysis showed a reduced rate of diabetes amongst patients with CAE compared to those without (OR 0.65, p<0.0001). Conclusion: Our findings suggested that diabetes might play a protective role for the development of CAE, indicating that further study is needed to evaluate the association diabetes and CAE including underlying mechanisms and future medical interventional strategies.

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Hyperglycemia modulates plasminogen activator inhibitor-1 expression and aortic diameter in experimental aortic aneurysm disease

Cited by 77 publications

References 25 publications

Oral Steroid Use and Abdominal Aortic Aneurysm Expansion　― Positive Association ―

Oral Steroid Use and Abdominal Aortic Aneurysm Expansion　― Positive Association ―

Increased PAI-1 in females compared with males is protective for abdominal aortic aneurysm formation in a rodent model

Relation of diabetes to coronary artery ectasia: A meta-analysis study

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Hyperglycemia modulates plasminogen activator inhibitor-1 expression and aortic diameter in experimental aortic aneurysm disease

Cited by 77 publications

References 25 publications

Oral Steroid Use and Abdominal Aortic Aneurysm Expansion ― Positive Association ―

Oral Steroid Use and Abdominal Aortic Aneurysm Expansion ― Positive Association ―

Increased PAI-1 in females compared with males is protective for abdominal aortic aneurysm formation in a rodent model

Relation of diabetes to coronary artery ectasia: A meta-analysis study

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Oral Steroid Use and Abdominal Aortic Aneurysm Expansion　― Positive Association ―

Oral Steroid Use and Abdominal Aortic Aneurysm Expansion　― Positive Association ―