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1.
Atherosclerosis ; 206(2): 362-8, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19368925

ABSTRACT

OBJECTIVES: To assess the role of coronary vasa vasorum (VV) spatial distribution in determining the location of early atherosclerotic lesion development. METHODS AND RESULTS: Six, 3-month-old, female, crossbred swine were fed 2% high-cholesterol (HC) diet for 3 months prior to euthanasia. Six other pigs were fed normal diet (N) for the entire 6 months. Right coronary arteries were harvested and scanned intact with micro-CT (20mum cubic-voxel-size). After scanning, randomly selected cross-sectional histological sections were stained for nuclear-factor kappaB (NF-kappaB), hypoxia-inducible factor-1alpha (HIF-1alpha), macrophages, von-Willebrand-factor, dihydroethidium (DHE), tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). The number of positive stained cells, as well as intima-to-media ratio, were compared with VV density (#/mm(2)) obtained from micro-CT images (which closely matched the location of the histological sections) in each of four equal quadrants of the coronary vessel wall. In normal, as well as HC pigs, the number of NF-kappaB (r=0.73 and 0.70), HIF-1alpha (r=0.74 and 0.77), TNF-alpha (r=0.58 and 0.72) and IL-6 (r=0.70 and 0.72) positive cells as well as the expression of DHE (Kendall tau coefficient -0.64 and -0.63) inversely correlated with VV density. In HC the VV density also inversely correlated with intima/media ratios (r=0.65). CONCLUSIONS: Our data suggest that low VV density territories within the coronary vessel wall are susceptible to hypoxia, oxidative stress and microinflammation and may therefore be starting points of early atherogenesis.


Subject(s)
Atherosclerosis/pathology , Tunica Intima/pathology , Vasa Vasorum/pathology , Animals , Cholesterol, Dietary/pharmacology , Coronary Vessels/drug effects , Coronary Vessels/pathology , Female , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Interleukin-6/metabolism , NF-kappa B/metabolism , Superoxides/metabolism , Swine , Tumor Necrosis Factor-alpha/metabolism , Tunica Intima/metabolism
2.
J Neural Transm Suppl ; (70): 147-51, 2006.
Article in English | MEDLINE | ID: mdl-17017522

ABSTRACT

Study of the nongenetic causes of Parkinson's disease (PD) was encouraged by discovery of a cluster of parkinsonism produced by neurotoxic pyridine 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the 1980s. Since that time, epidemiologic investigations have suggested risk factors, though their results do not establish causality. Pesticide exposure has been associated with increased risk in many studies. Other proposed risks include rural residence and certain occupations. Cigarette smoking, use of coffee/caffeine, and non-steroidal antiinflammatory drugs (NSAIDs) all appear to lower risk of PD, while dietary lipid and milk consumption, high caloric intake, and head trauma may increase risk. The cause of PD is likely multifactorial. Underlying genetic susceptibility and combinations of risk and protective factors likely all contribute. The combined research effort by epidemiologists, geneticists, and basic scientists will be needed to clarify the cause(s) of PD.


Subject(s)
Parkinson Disease/genetics , Animals , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Environmental Exposure/adverse effects , Environmental Pollutants/adverse effects , Humans , Occupational Exposure , Parkinson Disease/epidemiology , Parkinson Disease/etiology , Parkinson Disease, Secondary/chemically induced , Parkinson Disease, Secondary/epidemiology , Parkinson Disease, Secondary/pathology , Pesticides/adverse effects
3.
Kidney Int ; 70(5): 830-2, 2006 Sep.
Article in English | MEDLINE | ID: mdl-16929332

ABSTRACT

The main goal in the treatment of obstructive atherosclerotic renovascular disease (ARVD) is to preserve or recover renal function. The ARVD kidney continues to deteriorate in 20-40% of cases despite restoration of blood flow. Holden et al. report that renal function stabilized or improved in up to 97% of patients with the use of a distal embolic protection device.


Subject(s)
Angioplasty, Balloon/methods , Atherosclerosis/complications , Atherosclerosis/therapy , Embolism/prevention & control , Renal Artery Obstruction/therapy , Angioplasty, Balloon/adverse effects , Angioplasty, Balloon/instrumentation , Catheterization/instrumentation , Catheterization/methods , Disease Progression , Humans , Kidney/blood supply , Kidney/physiopathology , Regional Blood Flow/physiology , Renal Artery Obstruction/physiopathology , Stents
4.
Kidney Int ; 69(2): 266-71, 2006 Jan.
Article in English | MEDLINE | ID: mdl-16408115

ABSTRACT

Patients with chronic kidney disease (CKD) have increased risk for cardiovascular events. However, the association between these pathophysiological processes is unclear. Therefore, this study was designed to determine the association between early CKD and coronary microvascular disease in patients with normal or mildly diseased coronary arteries. A total of 605 patients with normal or mildly diseased coronary arteries based on angiography underwent coronary flow reserve (CFR) evaluation using intracoronary adenosine. Patients were divided based on glomerular filtration rate (GFR). CKD was defined as calculated GFR<60 ml/min/1.73 m(2). Patients with normal GFR (> or =60 ml/min/1.73 m(2), n=481) had higher CFR compared to those with CKD (n=124, CFR=3.0+/-0.8 vs 2.6+/-0.6, P<0.001, respectively). Patients with abnormal GFR were more likely to be older and of female gender, with greater prevalence of hypertension. Multiple logistic regression analysis adjusted for the aforementioned risk factors further supported the observed relationship. The current study shows that reduced renal function is associated with attenuated coronary vasodilator capacity in patients without obstructive coronary artery disease. The correlation between low GFR and reduced CFR may suggest parallel alterations in the renal and coronary microcirculation at the early stage of disease. Impairment in both microcirculatory beds may reflect an unmeasured risk factor induced by blunted renal function and add a burden to the increased propensity for cardiovascular events in CKD.


Subject(s)
Coronary Circulation , Coronary Disease/physiopathology , Renal Insufficiency/physiopathology , Adult , Aged , Chronic Disease , Female , Humans , Male , Microcirculation , Middle Aged , Risk Factors
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