Abstract:
:Background Expression of receptor for advanced glycation end products (RAGE) plays an important role in diabetic peripheral artery disease. We proposed to show that treatment with an antibody blocking RAGE would improve hind limb perfusion and muscle viability in diabetic pig with femoral artery (FA) ligation. Methods and Results Purpose-bred diabetic Yucatan minipigs with average fasting blood sugar of 357 mg/dL on insulin to maintain a glucose range of 300 to 500 mg/dL were treated with either a humanized monoclonal anti-RAGE antibody (CR-3) or nonimmune IgG. All pigs underwent intravascular occlusion of the anterior FA. Animals underwent (201Tl) single-photon emission computed tomography/x-ray computed tomography imaging on days 1 and 28 after FA occlusion, angiogenesis imaging with [99mTc]dodecane tetra-acetic acid-polyethylene glycol-single chain vascular endothelial growth factor (scVEGF), muscle biopsies on day 7, and contrast angiogram day 28. Results showed greater increases in perfusion to the gastrocnemius from day 1 to day 28 in CR-3 compared with IgG treated pigs (P=0.0024), greater uptake of [99mTc]dodecane tetra-acetic acid-polyethylene glycol-scVEGF (scV/Tc) in the proximal gastrocnemius at day 7, confirmed by tissue staining for capillaries and vascular endothelial growth factor A, and less muscle loss and fibrosis at day 28. Contrast angiograms showed better reconstitution of the distal FA from collaterals in the CR-3 versus IgG treated diabetic pigs (P=0.01). The gastrocnemius on nonoccluded limb at necropsy had higher 201Tl uptake (percentage injected dose per gram) and reduced RAGE staining in arterioles in CR-3 treated compared with IgG treated animals (P=0.04). Conclusions A novel RAGE-blocking antibody improved hind limb perfusion and angiogenesis in diabetic pigs with FA occlusion. Contributing factors are increased collaterals and reduced vascular RAGE expression. CR-3 shows promise for clinical treatment in diabetic peripheral artery disease.
journal_name
J Am Heart Assocjournal_title
Journal of the American Heart Associationauthors
Johnson LL,Johnson J,Ober R,Holland A,Zhang G,Backer M,Backer J,Ali Z,Tekabe Ydoi
10.1161/JAHA.120.016696subject
Has Abstractpub_date
2021-01-05 00:00:00pages
e016696issue
1issn
2047-9980journal_volume
10pub_type
杂志文章abstract:BACKGROUND:Metformin use reduces the incidence and severity of stroke in patients with type 2 diabetes mellitus (DM). The benefits of metformin for stroke have not been examined in hemodialysis patients with DM. METHODS AND RESULTS:Using the National Health Insurance Research Database, we identified 17 760 patients wi...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章,多中心研究
doi:10.1161/JAHA.117.007611
更新日期:2017-11-16 00:00:00
abstract::Background Circulating proteins are exposed to vascular endothelial layer and influence their functions. Among them, adipsin is a member of the trypsin family of peptidases and is mainly secreted from adipocytes, monocytes, and macrophages, catalyzing the rate-limiting step of the alternative complement pathway. Howev...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.119.013716
更新日期:2019-12-03 00:00:00
abstract::Background We aimed to determine the change in treatment strategies and times to treatment over the first 5 years of the Mission: Lifeline program. Methods and Results We assessed pre- and in-hospital care and outcomes from 2008 to 2012 for patients with ST -segment-elevation myocardial infarction at US hospitals, usi...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章,多中心研究
doi:10.1161/JAHA.118.008096
更新日期:2019-01-08 00:00:00
abstract::Background Coronary artery disease remains a major cause of death despite better outcomes of ST-segment-elevation myocardial infarction (STEMI). We aimed to analyze data from the Ruti-STEMI registry of in-hospital, 28-day, and 1-year events in patients with STEMI over the past 3 decades in Catalonia, Spain, to assess ...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.120.017159
更新日期:2020-10-20 00:00:00
abstract:BACKGROUND:The scientific evidence base in support of population-wide salt reduction is strong, but current high-quality data about salt intake levels in India are mostly absent. This project sought to estimate daily salt consumption levels in selected communities of Delhi and Haryana in north India and Andhra Pradesh ...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.116.004547
更新日期:2017-01-06 00:00:00
abstract::Background Dietary micronutrient deficiencies have been shown to predict event-free survival in other countries but have not been examined in patients with heart failure living in the United States. The purpose of this study was to determine whether number of dietary micronutrient deficiencies in patients with heart f...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.117.007251
更新日期:2018-09-04 00:00:00
abstract:BACKGROUND:Pediatric syncope is common. Cardiac causes are rarely found. We describe and assess a pragmatic approach to these patients first seen by a pediatric cardiologist in the New England region, using Standardized Clinical Assessment and Management Plans (SCAMPs). METHODS AND RESULTS:Ambulatory patients aged 7 t...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章,多中心研究
doi:10.1161/JAHA.115.002931
更新日期:2016-02-19 00:00:00
abstract:BACKGROUND:Diabetes is associated with coronary arteriolar endothelial dysfunction. We investigated the role of the small/intermediate (SK(Ca)/IK(Ca)) conductance of calcium-activated potassium channels in diabetes-related endothelial dysfunction. METHODS AND RESULTS:Coronary arterioles (80 to 150 μm in diameter) were...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.115.002062
更新日期:2015-08-24 00:00:00
abstract:BACKGROUND:Ticagrelor is a P2Y12 receptor inhibitor used in acute coronary syndromes to reduce platelet activity and to decrease thrombus formation. Ticagrelor is associated with a reduction in mortality incremental to that observed with clopidogrel, potentially related to its non-antiplatelet effects. Evidence from an...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章,随机对照试验
doi:10.1161/JAHA.117.005894
更新日期:2017-05-02 00:00:00
abstract::Background Systemic innate immune priming is a recognized sequela of post-ischemic neuroinflammation and contributor to delayed neurodegeneration. Given mounting evidence linking acute stroke with reactive lung inflammation, we asked whether enhanced expression of the endogenous antioxidant extracellular superoxide di...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.118.011801
更新日期:2019-05-07 00:00:00
abstract:BACKGROUND:Cryoballoon pulmonary vein isolation (PVI) has emerged as an alternative to radiofrequency PVI for atrial fibrillation (AF). Data are lacking to define the rates and predictors of complications, particularly phrenic nerve injury (PNI). METHODS AND RESULTS:We evaluated a single-center prospective registry of...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.116.003724
更新日期:2016-07-21 00:00:00
abstract::Background Angiotensin II type 1 receptor ( AT 1R) autoantibody ( AT 1- AA ) was first identified as a causative factor in preeclampsia. Unlike physiological ligand angiotensin II (Ang II ), AT 1- AA can induce vasoconstriction in a sustained manner, causing a series of adverse effects, such as vascular injury and poo...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.118.011179
更新日期:2019-03-19 00:00:00
abstract:BACKGROUND:This study aimed to determine the relationship of statin therapy and cardiovascular risk factors to changes in atherosclerosis in the carotid artery. METHODS AND RESULTS:Carotid magnetic resonance imaging was used to evaluate 106 hyperlipidemic participants at baseline and after 12 months of 3-hydroxy-3-met...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.116.003621
更新日期:2016-07-13 00:00:00
abstract::Background Both genetic and nongenetic factors can predispose individuals to cardiovascular risk. Finding ways to alter these predispositions is important for cardiovascular disease prevention. Methods and Results We used a novel whole-genome approach to estimate the genetic and nongenetic effects on-and hence their p...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.119.015661
更新日期:2020-04-21 00:00:00
abstract:BACKGROUND:Cardiac sodium channel (NaV1.5) dysfunction contributes to arrhythmogenesis during pathophysiological conditions. Nav1.5 localizes to distinct subcellular microdomains within the cardiomyocyte, where it associates with region-specific proteins, yielding complexes whose function is location specific. We herei...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.117.007622
更新日期:2017-12-08 00:00:00
abstract:BACKGROUND:We studied (1) the rates of stroke or systemic embolism and bleeding in patients with atrial fibrillation and peripheral artery disease (PAD) and (2) the efficacy and safety of apixaban versus warfarin in patients with atrial fibrillation with and without PAD. METHODS AND RESULTS:The Apixaban for Reduction ...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.116.004699
更新日期:2017-01-17 00:00:00
abstract::Background Sex-specific differences may influence prognosis after deferred revascularization following fractional flow reserve (FFR) measurement. This study sought to investigate the sex differences in long-term prognosis of patients with deferred revascularization following FFR assessment. Methods and Results A total...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.119.014458
更新日期:2020-02-18 00:00:00
abstract:BACKGROUND:Peripheral arterial disease (PAD) shares several risk factors with atrial fibrillation (AF), and persons with PAD have an increased risk of stroke. It is unclear if PAD is associated with an increased risk for AF and whether this potential association explains the increased risk of stroke observed in those w...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章,多中心研究
doi:10.1161/JAHA.114.001270
更新日期:2014-11-17 00:00:00
abstract::Background Higher fibroblast growth factor-23 ( FGF -23) levels are associated with incident heart failure ( HF ) in MESA (the Multiethnic Study of Atherosclerosis). FGF -23 is also associated with left ventricular hypertrophy. Whether the FGF -23 association with HF is similar for heart failure with reduced ejection ...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章,多中心研究
doi:10.1161/JAHA.117.008334
更新日期:2018-09-18 00:00:00
abstract:BACKGROUND:Contemporary rates of oral anticoagulant (OAC) therapy and associated outcomes among patients undergoing percutaneous coronary intervention (PCI) have been poorly described. METHODS AND RESULTS:Using data from an integrated health care system from 2009 to 2014, we identified patients on OACs within 30 days ...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.116.004310
更新日期:2016-10-17 00:00:00
abstract::Congenital heart disease is the most common congenital defect observed in newborns. Within the spectrum of congenital heart disease are left-sided obstructive lesions (LSOLs), which include hypoplastic left heart syndrome, aortic stenosis, bicuspid aortic valve, coarctation of the aorta, and interrupted aortic arch. T...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.120.019006
更新日期:2021-01-19 00:00:00
abstract:BACKGROUND:Postural tachycardia syndrome (POTS) is a disorder of chronic orthostatic intolerance accompanied by excessive orthostatic tachycardia. Patients with POTS commonly have comorbid conditions such as attention deficit hyperactivity disorder, depression, or fibromyalgia that are treated with medications that inh...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章,随机对照试验
doi:10.1161/JAHA.113.000395
更新日期:2013-09-03 00:00:00
abstract:BACKGROUND:Tissue Doppler index E/e' is used clinically and in multidisciplinary research for estimation of left ventricular filling pressure (LVFP) and diastolic dysfunction (DD)/heart failure with preserved ejection fraction (HFpEF). Its diagnostic accuracy is not well studied. METHODS AND RESULTS:From the PubMed, S...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章,meta分析,评审
doi:10.1161/JAHA.115.002530
更新日期:2016-01-25 00:00:00
abstract:BACKGROUND:Elevated albuminuria as well as an increased serum uric acid concentration is associated with poor cardiovascular outcome. We questioned whether these 2 variables (albuminuria and serum uric concentration) may be interrelated via tubular uric acid reabsorption. METHODS AND RESULTS:Included were 7688 partici...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/jaha.113.000613
更新日期:2014-01-01 00:00:00
abstract:BACKGROUND:The increased adverse cardiac events in women undergoing coronary artery bypass grafting are multifactorial and may include clinical, psychosocial, and biological factors. Potential contributing biological factors could include vascular hyperreactivity of the internal mammary artery (IMA) to endogenous vasoc...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.117.007126
更新日期:2018-07-09 00:00:00
abstract:BACKGROUND:Periaortic fat, because of its contiguity with the aorta, may promote vascular remodeling and aortic dilatation. However, the relations between perioartic fat depots and aortic dimensions have not been previously described. METHODS AND RESULTS:A total of 3001 individuals (mean age 50 ± 10 years, 49% women) ...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.112.000885
更新日期:2012-12-01 00:00:00
abstract:BACKGROUND:Accumulated research has shown that the older adult brain is significantly more vulnerable to stroke than the young adult brain. Although recent evidence in young adult rats demonstrates that single-whisker stimulation can result in complete protection from ischemic damage after permanent middle cerebral art...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.112.001255
更新日期:2012-08-01 00:00:00
abstract:BACKGROUND:Long chain acyl-CoA synthetases (ACSL) catalyze long-chain fatty acids (FA) conversion to acyl-CoAs. Temporal ACSL1 inactivation in mouse hearts (Acsl1(H-/-)) impaired FA oxidation and dramatically increased glucose uptake, glucose oxidation, and mTOR activation, resulting in cardiac hypertrophy. We used unb...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.114.001136
更新日期:2015-02-24 00:00:00
abstract:BACKGROUND:Although several risk factors for acute kidney injury (AKI) have been identified, early detection of AKI in acute decompensated heart failure patients remains a challenge. The aim of this study was to develop and validate a risk score for early prediction of AKI in acute decompensated heart failure patients....
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.116.004035
更新日期:2016-11-16 00:00:00
abstract:BACKGROUND:Hospital procedures have been associated with cognitive change in older patients. This study aimed to document the prevalence of mild cognitive impairment in individuals undergoing left heart catheterization (LHC) before the procedure and the incidence of cognitive decline to 3 months afterwards. METHODS AN...
journal_title:Journal of the American Heart Association
pub_type: 杂志文章
doi:10.1161/JAHA.117.008004
更新日期:2018-03-10 00:00:00