Vascular Disease In Type Research Articles

Five-year follow-up observation of interventional therapy for lower extremity vascular disease in type 2 diabetes and analysis of risk factors for restenosis.

The high incidence of type 2 diabetes, the low rate of compliance, and the complex mechanism of vascular disease caused by diabetes make its complications increase year by year. Our study aimed to investigate the clinical characteristics of lower extremity vascular diseases in type 2 diabetes and evaluate the long-term efficacy of vascular intervention for these diseases. From 2007 to 2014, 362 patients who underwent vascular intervention in our hospital due to lower extremity vascular diseases in type 2 diabetes were followed up for 5 years and their clinical characteristics were analyzed in this retrospective study. Compared with those before treatment, the values of blood pressure, fasting blood glucose, glycated hemoglobin (HbA1c), total cholesterol (TC), triglyceride Ester (TG), and low density lipoprotein-cholesterol (LDL-C) of patients were significantly lower 5 years after intervention (P < 0.01). We found that the levels of fibrinogen, blood glucose, HbA1c, TC, TG, LDL-C, and small dense low-density lipoprotein (sdLDL) in the vascular restenosis group were significantly higher than those in the vascular patency group (P < 0.001), whereas the level of HDL-C in the vascular restenosis group was significantly lower compared with the vascular patency group. Vascular intervention can significantly improve a series of biochemical indicators in patients with lower extremity vascular diseases caused by type 2 diabetes. Postoperative restenosis may be related to hypertension, duration of diabetes, rate of inferior knee disease, fibrinogen, and sdLDL. Good survival and limb salvage were achieved in the patients in this series with interventions and medical treatment provided by endocrinologists.

12(S)-HETE mediates diabetes-induced endothelial dysfunction by activating intracellular endothelial cell TRPV1

Patients with diabetes develop endothelial dysfunction shortly after diabetes onset that progresses to vascular disease underlying the majority of diabetes-associated comorbidities. Increased lipid peroxidation, mitochondrial calcium overload, and mitochondrial dysfunction are characteristics of dysfunctional endothelial cells in diabetic patients. We here identified that targeting the lipid peroxidation product 12(S)-hydroxyeicosatetraenoic acid-induced [12(S)-HETE-induced] activation of the intracellularly located cation channel transient receptor potential vanilloid 1 (TRPV1) in endothelial cells is a means to causally control early-stage vascular disease in type I diabetic mice. Mice with an inducible, endothelium-specific 12/15-lipoxygenase (12/15Lo) knockout were protected similarly to TRPV1-knockout mice from type 1 diabetes-induced endothelial dysfunction and impaired vascular regeneration following arterial injury. Both 12(S)-HETE in concentrations found in diabetic patients and TRPV1 agonists triggered mitochondrial calcium influx and mitochondrial dysfunction in endothelial cells, and 12(S)-HETE effects were absent in endothelial cells from TRPV1-knockout mice. As a therapeutic consequence, we found that a peptide targeting 12(S)-HETE-induced TRPV1 interaction at the TRPV1 TRP box ameliorated diabetes-induced endothelial dysfunction and augmented vascular regeneration in diabetic mice. Our findings suggest that pharmacological targeting of increased endothelial lipid peroxidation can attenuate diabetes-induced comorbidities related to vascular disease.

The relation of serum endocan and soluble endoglin levels with metabolic control in children and adolescents with type 1 diabetes mellitus.

Objectives Endothelial dysfunction is an early marker of vascular disease in Type 1 diabetes mellitus (T1DM). In the present study, we aimed to investigate serum endocan and soluble endoglin (S-endoglin) levels, and their relation with metabolic control in children with T1DM, which was not previously assessed. Methods A total of 64 T1DM subjects and 64 healthy subjects were included in this study. Their anthropometric features, arterial blood pressures, pubertal status, insulin doses were recorded. Glycated hemoglobin, serum endocan and S-endoglin levels were measured and compared to each other. Results Serum endocan and S-endoglin levels were higher in children with T1DM than those of healthy group (p<0.01). Significant positive correlation was detected between both endocan and S-endoglin (r=0.579, p<0.001); and HbA1c and endocan (r=0.296, p=0.01). Compared to patients with good metabolic control, those with poorer metabolic control (HbA1c > 8%) had an older age, longer duration of diabetes, higher number of pubertal children. Also, patients with poorer metabolic control had higher endocan and S-endoglin levels than those of healthy group, but this finding did not reach statistical significance. There was no correlation between the endocan/S-endoglin levels and age, duration of diabetes and insulin dose. Conclusion Serum levels of endocan and S-endoglin which are novel biomarkers of endothelial dysfunction are high in children with T1DM. Elevated serum endocan and endoglin levels in children with T1DM without microvascular complications indicates endothelial damage in very early stages of the disease.

To determine if digital pulse oximetry is an acceptable screening tool for asymptomatic peripheral vascular disease in type 2 diabetes mellitus: An observational study

Methods: The present analytical cross-sectional study was carried out among 80 patients of type 2 Diabetes Mellitus with asymptomatic PVD were included. The diagnostic accuracy of Ankle-Brachial Index (ABI) and pulse oximetry as a screening tool was compared against Color Doppler ultrasonography as the reference standard.

Aortic dissection – Ultrasound and doppler diagnosis

Aortic dissection is the most common form of acute aortic syndromes and a type of vascular disease. It occurs when blood enters the medial layer of the aortic wall through a tear or penetrating ulcer in the intima and tracks along the media, forming a second blood-filled channel within the wall. On grey-scale ultrasound (USG), the transverse image of the abdominal aorta shows a vertical linear hyperechoic structure, which represents the dissected intima. On color Doppler, there is a flow on both sides of the dissected intima indicating flow in the false and true lumen. Thus, aortic dissection is easily and readily diagnosed on USG, which is the most widely available investigation, making the availability of early treatment option to a patient.

Vascular Diseases In Patients With Chronic Myeloproliferative Neoplasms - Impact Of Comorbidity.

BackgroundPatients with chronic myeloproliferative neoplasms (MPNs), including essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF), are at high risk of vascular complications. However, the magnitude of this is risk not well known and the possible effect of comorbidity is poorly understood.AimOur aim was to compare the risk of vascular diseases in patients with MPNs and matched comparisons from the general population and to study the effect modification of comorbidity.MethodsWe followed 3087 patients with ET, 6076 with PV, 3719 with PMF or unspecified MPN, and age- and sex-matched general population comparisons to estimate the risks of cardiovascular diseases such as myocardial infarction and stroke. We computed 5-year cumulative incidences (risks) for vascular disease in patients with MPNs and comparisons as well as 1-year and 5-year risks, risk differences, and hazard ratios (HRs) for vascular diseases comparing rates in each group of patients with their comparison cohort by level of comorbidity based on the Charlson Comorbidity Index (CCI) [score of 0 (low comorbidity), of 1–2 (moderate comorbidity), and of >2 (severe comorbidity)], as well as other comorbid conditions.ResultsThe overall 5-year risk of vascular disease ranged from 0.5% to 7.7% in patients with MPNs, which was higher than the risk in the general population. In the same period, the adjusted HRs for vascular disease were 1.3 to 3.7 folds higher in patients with MPNs compared to the general population. An increase in CCI score was associated with an equally increased rate of most types of vascular diseases during the first 5 years of follow-up in both MPN and comparisons.ConclusionPatients with MPNs have a higher risk of vascular diseases during the first 5 years than that of the general population; however, comorbidity modifies the rates similarly in MPN and in the general population.

Vitamin D and cause-specific vascular disease and mortality: a Mendelian randomisation study involving 99,012 Chinese and 106,911 European adults

BackgroundRandomised control trials and genetic analyses have demonstrated that vitamin D or 25-hydroxyvitamin D (25[OH]D) levels may not play a causal role in the development of cardiovascular disease. However, it is unclear if 25(OH)D is causally associated with cause-specific vascular disease and lipids. Therefore, we examined the causal association of 25(OH)D with myocardial infarction, stroke, ischaemic heart disease, ischaemic stroke, subarachnoid haemorrhage, intracerebral haemorrhage, and lipid levels among both Chinese and Europeans.MethodsWe used a Mendelian randomisation (MR) design in the China Kadoorie Biobank, the Copenhagen City Heart Study, and the Copenhagen General Population Study. The 25(OH)D-related genetic variants in the CYP2R1 and DCHR7 genes were genotyped in 99,012 Chinese adults and 106,911 Danish adults.ResultsIn Chinese adults, plasma 25(OH)D levels were not significantly associated with cause-specific vascular disease or mortality, with the exception of intracerebral haemorrhage (HR, 1.09 [95% CI, 1.01,1.18] per 25 nmol/L higher plasma 25(OH)D). In Europeans, plasma 25(OH)D levels were inversely associated with all types of vascular diseases and mortality. However, MR analysis did not demonstrate causal associations of genetically increased 25(OH)D levels with cause-specific vascular diseases, or mortality in both Chinese and European adults. In addition, each 25 nmol/L higher 25(OH)D was observationally associated with lower total cholesterol and low-density lipoprotein cholesterol levels, but higher high-density lipoprotein cholesterol levels. Likewise, MR analysis showed that 25(OH)D levels were not causally associated with lipids in both Chinese and European adults after Bonferroni correction.ConclusionsWe found no evidence to support that genetically increased 25(OH)D was associated with a lower risk of ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, and lipid levels in both Chinese and European adults. These results suggest that the inverse associations of vitamin D with vascular disease could be the result of confounding.

Comparative study of pulse oximetry and ankle-brachial index as a screening test for asymptomatic peripheral vascular disease in type 2 diabetes mellitus against color doppler ultrasonography as reference standard

Background: Currently about 35 million Indians are reported to suffer from diabetes mellitus, a significant proportion of whom are either undiagnosed or diagnosed but undertreated leading to poor glycemic control. This leads to accelerated development of macrovascular complications like Peripheral Vascular Disease (PVD). As most of the patients are asymptomatic, hence, early detection and treatment of PVD in patients with diabetes mellitus carries utmost importance.Methods: The present study was undertaken in SGRDIMSAR, Amritsar on 100 patients of type 2 Diabetes Mellitus with asymptomatic PVD. The diagnostic accuracy of Ankle-Brachial Index (ABI) and pulse oximetry as a screening tool was compared against Color Doppler ultrasonography as the reference standard.Results: The sensitivity, specificity, positive predictive value and negative predicted value of pulse oximetry to diagnose asymptomatic PVD in diabetics was found to be 98.31% (95% CI: 90.91-99.96), 41.46% (95% CI: 26.32- 57.89), 70.73% (95% CI: 65.08-75.81) and 94.44% (95%CI: 70.19-99.19) respectively. The sensitivity, specificity, positive predictive value and negative predicted value of ABI to diagnose asymptomatic PVD in diabetics was found to be 77.97% (95% CI: 65.27-87.71), 97.56% (95% CI: 87.14-99.94), 97.87% (95% CI: 86.85-99.69) and 75.47% (95% CI: 65.51-83.29) respectively.Conclusions: Pulse oximetry is better than ABI for the screening for asymptomatic PVD among diabetics. However, ABI is more accurate as compared to pulse oximetry in diagnosing asymptomatic PVD in diabetics.

Correlation of Ankle Brachial Index with Peripheral Vascular Disease in Type 2 Diabetes Mellitus

Objective : The aim of this study was to correlate ankle brachial index (ABI) with peripheral vascular disease (PVD) in type 2 diabetes mellitus . Material and methods : This was a hospital based interdisciplinary prospective study. A total of 100 patients in the age group of 30 to 80 years having peripheral vascular disease with predefined inclusion criteria were included in the study. Patients with other causes of raised blood sugar or peripheral vascular disease were excluded by relevant investigations. Ankle Brachial Index (ABI) was calculated using sphygmomanometer, and Colour Doppler Ultrasound (CDU) was used to diagnose PVD. Both the ABI method and the CDU method were compared for detecting PVD. Results : In our study, mean age was 60.04 ± 5.03 years, mean body mass index was 27.10 ± 2.67 kg/m2 and mean duration of diabetes was 7.75 ± 1.50 years. Among the 68 diagnosed cases of PVD on CDU, 70.6% cases were detected to have PVD by the ABI method (true positive) whereas 20 (29.4%) cases remained undiagnosed when ABI alone was used for the diagnosis (false negative). Conversely, among 51 diagnosed cases of PVD by ABI method 5.9% cases were found to be normal on CDU (false positive). The ABI method was found to have specificity of 88.5% but the sensitivity was only 70.6%. Conclusion: ABI has a very high specificity but the sensitivity is low compared to colour Doppler ultrasound. Therefore, if ABI is abnormal, the diagnosis of PVD is almost certain but in symptomatic cases with normal ABI; colour Doppler should be performed to exclude the PVD. Keywords : Ankle Brachial Index, peripheral vascular disease, Colour Doppler Ultrasound, type 2 diabetes mellitus. DOI : 10.7176/JMPB/57-02 Publication date : July 31 st 2019

783-P: Correlations between Serum 25-Hydroxy Vitamin D and Vascular Disease in Type 2 Diabetics

Objective: Vascular lesions caused by type 2 diabetes (T2DM) is unquestionable, but the relationship with serum 25-hydroxyvitamin D (25(OH)D) is controversial. Our study intends to analyze the association between the vascular disease of T2DM and the level of 25(OH)D. Methods: A total of 576 patients with T2DM and 532 healthy people in our hospital from 2016 to 2017 were enrolled. The level of 25(OH)D between T2DM group and non-DM group was compared. Patients with T2DM were divided into carotid intimal thickening group(472 cases, IMT&amp;gt;1.0mm) and normal carotid artery group(104 cases, IMT&amp;lt;1.0mm) by ultrasonography. According to whether hemorrhage or exudation in fundus photography, they were divided into microvascular disease group(226 cases) and non-microvascular disease group(350 cases). Furthermore, we analyzed the association between the level of 25(OH)D and clinical characters by SPSS22.0. Results: The level of 25(OH)D in T2DM group was significantly lower than non-DM group(42.66±13.81 vs.66.00±11.53, P&amp;lt;0.001). Serum 25(OH)D concentration increased in carotid intimal thickening group(42.80±13.96 vs.42.07±13.16, P=0.626), but was lower in microvascular disease group(41.17±14.02 vs.43.63±13.60, P=0.036). Levels of HbA1c, FPG, FINS, FCP, Alanine aminotransferase, Aspartate aminotransferase, Creatinine, Uric acid, TC, TG, HOMA-IR in the low 25(OH)D group were higher than normal group, but HOMA-IS, HOMA-β were lower. Therein, levels of FPG(P=0.010), FCP(P=0.006), TC(P&amp;lt;0.001), TG(P&amp;lt;0.001), HOMA-IS(P=0.002)had significant difference. In addition, gender, age and duration of disease was not related to 25(OH)D. Conclusion: The 25(OH)D in patients with T2DM is lower than healthy people and the incidence of microvascular disease is increased, but there is no definite correlation with macrovascular disease. In the T2DM population, supplementation of 25(OH)D may improve vascular lesions by regulating glycolipid metabolism, which needs further study. Disclosure N. Li: None. L. Xu: None. Y. Wang: None. S. Yang: None. P. Yang: None. J. Dong: None. H. Li: None. S. Qu: None.

Total Adiponectin and Risk of Symptomatic Lower Extremity Peripheral Vascular Disease in Type 2 Diabetes Mellitus

Total Adiponectin and Risk of Symptomatic Lower Extremity Peripheral Vascular Disease in Type 2 Diabetes Mellitus

Recent trends over time in vascular disease in type 1 diabetes: insights from the Pittsburgh Epidemiology of Diabetes Complications study.

To evaluate recent trends, by diagnosis year, in the cumulative incidence of vascular type 1 diabetes (T1D) complications and their risk factors up to 35 years duration. Participants from the Epidemiology of Diabetes Complications study of childhood-onset T1D were categorized into three calendar year onset cohorts: 1965-69, 1970-74, and 1975-80. All-cause, cardiovascular and renal mortality were determined both on the complete cohort (n=440) as well as in the subset with clinical examinations (n=363). Coronary artery disease (CAD, CAD death, myocardial infarction, revascularization, angina and ischemic ECG abnormalities); lower extremity arterial disease (LEAD, abnormal Ankle Brachial Index/amputation/intermittent claudication); distal symmetric polyneuropathy (DSP, clinical exam); cardiac autonomic neuropathy (CAN, abnormal heart rate response to deep breathing); overt nephropathy (ON, albumin excretion rate>200 μg/min) and proliferative retinopathy (PR, fundus photography) were assessed on the subset with clinical examinations. While all-cause, cardiovascular and renal mortality improved with a more recent diagnosis in the overall cohort, no univariate differences were observed for complications requiring examination (CAD, DSP, CAN, ON), although a borderline trend toward improved complication-free survival with a more recent onset was observed for PR (p=0.06). LEAD incidence showed an anomalous pattern, being highest in the 1975-80 and lowest in the 1970-74 cohort (p=0.009). Allowing for risk factors over time did not materially change these results. Despite declines in all-cause, cardiovascular and renal mortality in the total cohort, no improvements were observed in either mortality or complication incidence with a more recent onset in the examined cohort.

The Side Effect of Haloperidol in Schizophrenic Patients: Analysis of Red Blood Cell Distribution Width (RDW) and Mean Platelet Volume (MPV) Values

INTRODUCTION: Like the increase of pro-inflammatory cytokines and oxidative stress as schizophrenia pathophysiology, haloperidol also increases RDW and MPV values. Both of these values ​​have been clinicians concern because they are a risk factor for the various type of vascular disease.&#x0D; &#x0D; OBJECTIVE: This study aims to determine the side effect of haloperidol on RDW and MPV values in schizophrenic patients. &#x0D; &#x0D; METHODS: This research method uses observational analytic design with a prospective cohort approach with pre and posts analysis conducted at the Regional Special Hospital of South Sulawesi Province during May - July 2018 in 30 schizophrenic subjects. The subjects were diagnosed as first episode schizophrenia based on ICD 10, blood samples were taken, for RDW and MPV values ​​before and after haloperidol was given at the 4th and 8th weeks.&#x0D; &#x0D; RESULTS: The results showed that the mean RDW value at the 4th week was higher in 15 mg/day haloperidol group (15.8) compared to 7.5 mg/day haloperidol group (15.3) with p&amp;lt;0.05. Mean RDW value taken at 8th week was higher in 15 mg/day haloperidol group (16.4) compared to 7.5 mg/day haloperidol group (15.6) with p&amp;lt;0.001. Mean MPV value taken at 8th week was higher in 15 mg/day haloperidol group (13.3) compared to 7.5 mg/day haloperidol group (11.6) with p&amp;lt;0.001. &#x0D; &#x0D; CONCLUSION: This study showed an increase in the RDW value in schizophrenia subjects prior to the haloperidol administration. RDW ​​and MPV values were higher after haloperidol treatment compares to before haloperidol treatment. The increase of RDW and MPV values tend to be influenced by haloperidol dosage and administration duration.

Vascular Genetics: Presentations, Testing, and Prognostics.

Numerous studies have begun to unravel the genetic basis of not only aortic disease but also other forms of commonly encountered vascular diseases. The goal of this review is to provide clinicians a reference to help identify and diagnose different types of vascular disease with a genetic underpinning. Ongoing studies have identified numerous genes involved in the TGF-β signaling pathway that are also associated with thoracic aortic aneurysm and dissection, and it is possible to test for pathogenic variants in these genes in the clinical setting using commercially available genetic testing panels. Additional studies have begun to identify genetic variants associated with an increased risk of bicuspid aortic valve, abdominal aortic aneurysm, and fibromuscular dysplasia. With increased availability of low-cost genetic testing, clinicians are now able to not only definitively diagnose some vascular syndromes but also provide information on the risk of disease in other family members, as well as provide guidance in terms of family planning. As the cost of genetic testing continues to drop with the benefit of increasing insurance coverage, genetic data will increasingly become part of clinical care for many patients with vascular disease.

Correlation between High Serum Uric Acid Levels with Occurrence of Diabetic Peripheral Neuropathy in Patients with Type 2 Diabetes Mellitus in Soetomo General Hospital

Background: The increased serum uric acid (SUA) levels have been linked to macro vascular disease in Type 2 Diabetes Melitus. The correlation between serum uric acid levels and diabetic peripheral neuropathy has not been addressed properly.&#x0D; Objective: The aim of this study was to determine the correlation between high serum uric acid levels and diabetic peripheral neuropathy.&#x0D; Methods: This was a case-control design study and the sampling was done consecutively by following the inclusion and the exclusion criteria. The diabetic peripheral neuropathy was evaluated using Electroneuromyography (EMNG) and the serum were taken for uric acid level examination. Chi square test was used for the correlation analysis.&#x0D; Result: Thirty subjects were enrolled and divided into an experimental group of 15 subjects and a control group of 15 subjects as well. We found that the diabetic peripheral neuropathy did not show a significant correlation with high serum uric acid levels, p=0,136 and OR 3,143 (CI 95% 0,681-14,503).&#x0D; Conclusions: There was no correlation between high serum uric acid levels with diabetic peripheral neuropathy.

Review of risk factors, treatment, and prevention of saphenous vein graft disease after coronary artery bypass grafting.

Saphenous vein graft disease (SVGD) is a type of vascular disease that may develop after coronary artery bypass grafting (CABG). SVGD seriously affects the short-term and long-term effects of CABG and increases the incidence of major adverse cardiovascular events. It is very important to identify patients at greatest risk and carry out prevention and treatment measures to determine the risk factors for SVGD. Many factors contribute to SVGD when the vein is grafted into an arterial environment, such as surgery-related factors, smoking, diabetes mellitus, hyperlipidemia, and others. In this review, we discuss the risk factors for SVGD, current surgical and pharmacologic therapies with which to manage SVGD, and the prevention of SVGD.

A clinical study of peripheral vascular diseases in type 2 diabetes mellitus

A clinical study of peripheral vascular diseases in type 2 diabetes mellitus

Increased ATP and ADO Overflow From Sympathetic Nerve Endings and Mesentery Endothelial Cells Plus Reduced Nitric Oxide Are Involved in Diabetic Neurovascular Dysfunction.

Since the mechanism of human diabetic peripheral neuropathy and vascular disease in type 1 diabetes mellitus remains unknown, we assessed whether sympathetic transmitter overflow is altered by this disease and associated to vascular dysfunction. Diabetes was induced by streptozotocin (STZ)-treatment and compared to vehicle-treated rats. Aliquots of the ex vivo perfused rat arterial mesenteric preparation, denuded of the endothelial layer, were collected to quantify analytically sympathetic nerve co-transmitters overflow secreted by the isolated mesenteries of both groups of rats. Noradrenaline (NA), neuropeptide tyrosine (NPY), and ATP/metabolites were detected before, during, and after electrical field stimulation (EFS, 20 Hz) of the nerve terminals surrounding the mesenteric artery. NA overflow was comparable in both groups; however, basal or EFS-secreted ir-NPY was 26% reduced (p < 0.05) in diabetics. Basal and EFS-evoked ATP and adenosine (ADO) overflow to the arterial mesentery perfusate increased twofold and was longer lasting in diabetics; purine tissue content was 37.8% increased (p < 0.05) in the mesenteries from STZ-treated group of rats. Perfusion of the arterial mesentery vascular territory with 100 μM ATP, 100 nM 2-MeSADP, or 1 μM UTP elicited vasodilator responses of the same magnitude in controls or diabetics, but the increase in luminally accessible NO was 60–70% lower in diabetics (p < 0.05). Moreover, the concentration–response curve elicited by two NO donors was displaced downwards (p < 0.01) in diabetic rats. Parallel studies using primary cultures of endothelial cells from the arterial mesentery vasculature revealed that mechanical stimulation induced a rise in extracellular nucleotides, which in the cells from diabetic rats was larger and longer-lasting when comparing the extracellular release of ATP and ADO values to those of vehicle-treated controls. A 5 min challenge with purinergic agonists elicited a cell media NO rise, which was reduced in the endothelial cells from diabetic rats. Present findings provide neurochemical support for the diabetes-induced neuropathy and show that mesenteric endothelial cells alterations in response to mechanical stimulation are compatible with the endothelial dysfunction related to vascular disease progress.

Mice expressing human apolipoprotein E4e exhibit altered thoracic ascending aortic elastic properties

Alzheimer's disease (AD) is characterized with the progressive loss of cognitive abilities that typically presents in the elderly population, therefore most research has focused primarily on the brain. Hypertension, obesity and atherosclerosis are often comorbidities that present with AD patients. Per the American Heart Association, by 2035 nearly half of the US population will suffer from some type of vascular disease. Despite that, peripheral vascular dysfunction within the progression of AD has not been studied in detail. Apolipoprotein‐ɛ (ApoE) is a lipid‐binding protein that is a major factor in cholesterol metabolism in the brain and periphery. ApoE is polymorphic and the expression of the ApoE4 allele is associated with late onset AD. Conversely, the ApoE3 allele has been shown to likely prevent neurodegeneration, suggesting a protective role for ApoE3 protein in the brain. In this study we investigated the functional (vasoconstriction &amp; vasodilation) and structural (elastin fiber organization and elasticity) properties of the aorta in 18‐month old mice expressing human ApoE4 or ApoE3, and wild type C57BL/6 mice using wire myography and conventional histological staining. Our data shows that phenylephrine‐induced contraction and acetylcholine‐induced vasodilation is not different among experimental groups. However, elastin fiber fragmentation and disorganization were observed within the aortic wall in ApoE4 mice as compared to age‐ and sex‐matched ApoE3 and C57BL/6 mice. Furthermore, the stretch‐induced wall stress and reversibility of elasticity were significantly reduced in aortic segments isolated from ApoE4 mice indicating an increase in aortic wall stiffness in ApoE4 mice. These data present the first evidence that neurodegenerative pathology in ApoE4 mice is associated with pathologic changes in the aortic wall that leads to increased vascular wall stiffness and reduced elasticity. This will establish a new direction aimed at studying the relationship between observed brain pathology in AD and abnormal changes in peripheral vascular function and structure that occur in a relevant mouse model for the disease.Support or Funding InformationThis study is supported by funding from Midwestern University Alzheimer's Advisory Committee.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Cell death-inducing DFF45-like effector C gene silencing alleviates pulmonary vascular remodeling in a type 2 diabetic rat model.

Aims/IntroductionCell death‐inducing DFF45‐like effector C (CIDEC) was proven to be closely associated with the development of insulin resistance and metabolic syndrome. We aimed to investigate whether CIDEC gene silencing could alleviate pulmonary vascular remodeling in a type 2 diabetes rat model.Materials and MethodsWe built a type 2 diabetes rat model. An adenovirus harboring CIDEC small interfering ribonucleic acid was then injected into the jugular vein to silence the CIDEC gene. After hematoxylin–eosin and Sirius red staining, we detected indexes of the pulmonary arterioles remodeling. Immunohistochemical staining of proliferating cell nuclear antigen was used to evaluate the pulmonary arterial smooth muscle cell proliferation. Apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling reaction and western blotting. The levels of signaling pathway proteins expression were measured by western blotting analyses.ResultsHistological analysis of the pulmonary artery showed that the thickness of the adventitia and medial layer increased notably in type 2 diabetes rats. Immunohistochemistry showed that more proliferating cell nuclear antigen‐positive pulmonary arterial smooth muscle cells could be seen in type 2 diabetes rats; and after CIDEC gene silencing, proliferating cell nuclear antigen positive cells decreased accordingly. Cleaved caspase‐3 and cleaved poly (adenosine diphosphate‐ribose) polymerase measured by western blotting showed increased apoptosis with overexpressed CIDEC in diabetes. Terminal deoxynucleotidyl transferase dUTP nick end labeling reaction showed that the apoptosis mainly occurred in endothelial cells. Western blotting analysis showed CIDEC overexpression in rats with diabetes, and phosphorylated adenosine 5′ monophosphate‐activated protein kinase‐α expression was significantly decreased. After CIDEC gene silencing, the expression of phosphorylated adenosine 5′ monophosphate‐activated protein kinase‐α was upregulated.ConclusionsThe CIDEC/5′ monophosphate‐activated protein kinase signaling pathway could be a potential therapeutic candidate against pulmonary vascular diseases in type 2 diabetes patients.