58 research outputs found
Inflammatory Mechanisms in Atherosclerosis: The Impact of Matrix Metalloproteinases
Inflammatory process is essential for the initiation and progression of
vascular remodeling, entailing degradation and reorganization of the
extra-cellular matrix (ECM) scaffold of the vessel wall, leading to the
development of atherosclerotic lesions. Matrix metalloproteinases (MMPs)
are zing dependent endo-peptidases found in most living organisms and
act mainly by degrading ECM components. Most MMPs are formed as inactive
proenzymes and are activated by proteolysis. This process depends and is
regulated by other proteases and endogenous MMP inhibitors (TIMPs). MMPs
and TIMPs play a major role not only in ECM degradation but also in
mediating cell migration, proliferation, tissue remodeling; acting as a
signal for the production and secretion of growth factors and cytokines.
More importantly MMPs through proteolysis and degradation of ECM
contribute in many physiological and pathological processes including
organ development, wound healing, tissue support, vascular remodeling
and restenosis, atherosclerosis progression, acute coronary syndromes,
myocardial infarction, cardiomyopathy, aneurysms remodeling, cancer,
arthritis, and chronic inflammatory diseases. A substantial body of
evidence support the notion that imbalance between the activity of MMPs
and their tissue inhibitors (TIMPs) contribute to the pathogenesis of
cardiovascular diseases such as atherosclerosis, vascular remodeling and
progression of heart failure. In this review, we will discuss the
relationship between MMPs, inflammation and atherosclerosis under the
topic of cardiovascular disease
Combined Invasive Peripheral Nerve Stimulation in the Management of Chronic Post-Intracranial Disorder Headache: A Case Report
The introduction of ventricular shunts dramatically changed the outcome and quality of life of hydrocephalic patients. However, shunt surgery continues to be associated with numerous adverse events. Headache is one of the most common complications after shunt operation. It is often of prolonged duration, the symptoms resemble those of migraine, and pain does not respond to medication. We propose invasive peripheral nerve stimulation as a potential solution in the treatment of patients suffering from chronic headache associated with shunted hydrocephalus. A young woman presented with daily holocephalic headache with diffuse pain exacerbated by lying down. Imaging revealed panventricular enlargement and possible aqueduct stenosis. When a ventriculoperitoneal shunt was placed, clinical symptoms resolved. Nevertheless, she gradually exacerbated after a second valve replacement due to wound infection. Imaging revealed decompressed ventricles and appropriate shunt placement. The diagnosis of chronic post-intracranial disorder headache was set. Therefore, occipital nerve stimulation was applied and, considering that the patient did not have a total response, bilateral parietal stimulation was added. Three months after the combined PNS, she experienced total remission of headache. Combined PNS eases refractory headaches much more than occipital nerve stimulation alone and could be considered as a solution for shunted hydrocephalus-associated headache
Vitamin D3, D2 and Arterial Wall Properties in Coronary Artery Disease
Objectives: There are two major forms of vitamin D, vitamin D2
(ergocalciferol) and vitamin D3 (cholecalciferol). We studied the effect
of the different vitamin D fractions (D3/D2) on arterial wall properties
in coronary artery disease (CAD) patients.
Methods: We included 252 subjects with CAD. Endothelial function was
evaluated by flow mediated dilation (FMD). Carotid femoral pulse wave
velocity (PWV) was measured as an index of arterial stiffness and
augmentation index (AI) as a measure of reflected waves. Measures for
25(OH)D2 and 25(OH)D3 were performed using Liquid Chromatography Mass
Spectrometry technology.
Results: From the study population, 155(62%), 66(26%) and 31(12%)
were categorized as having vitamin D deficiency, insufficiency and
sufficiency respectively. There was no difference between subjects with
vitamin D deficiency, insufficiency and sufficiency in FMD, AI and PWV
(p=NS for all). Subjects with vitamin D insufficiency/deficiency had
significantly higher D2 to D ratio compared to subjects with vitamin D
sufficiency. Interestingly, FMD was positively associated with D2 to D
ratio (rho=0.13, p=0.02) and subjects with D2 levels<0.3ng/ml had
impaired FMD compared to those with increased D2 levels (p=0.048).
Conclusion: Vitamin D insufficiency/deficiency is highly prevalent in
CAD subjects. Vitamin D2 concentrations are positively associated with
endothelial function. These findings may suggest a beneficial role of
vitamin D2 levels in vascular health
Clopidogrel response variability is associated with endothelial dysfunction in coronary artery disease patients receiving dual antiplatelet therapy
Objectives: Dual antiplatelet therapy with aspirin and a platelet P2Y12
ADP receptor antagonist is the cornerstone of treatment following
percutaneous coronary intervention (PCI). Several clinical and genetic
factors can cause suboptimal clopidogrel response. We examined the
impact of endothelial dysfunction on clopidogrel response variability in
subjects with stable coronary artery disease (CAD) after PCI.
Methods: We consecutively enrolled 198 patients with stable CAD one
month after successful PCI. All patients were receiving dual
antiplatelet therapy (clopidogrel 75 mg and aspirin 100 mg/day).
Platelet reactivity was measured by VerifyNow P2Y12 assay (Accumetrics,
San Diego, CA). VerifyNow reports its results in P2Y12 reaction units
(PRU) and the diagnostic cut-off value is 230. Endothelial function was
evaluated by flow mediated dilation (FMD).
Results: Patients with high on treatment platelet reactivity (32% of
the study population), compared to subjects with low on treatment
platelet reactivity, presented decreased FMD values (4.35 +/- 2.22% vs.
5.74 +/- 3.29%, p = 0.01). Moreover, an inverse association between
endothelial function measurement and platelet reactivity (r = -0.24, p =
0.001) was found. Importantly, multivariate analysis after adjustment
for age, gender and confounders revealed by the univariate analysis
(left ventricle ejection fraction, body mass index, diabetes,
dyslipidemia, coronary lesion number) showed that for every decrease in
FMD by 1% there is an anticipated increased in the odds of patients to
have HPR by 1.66 (95% CI 1.03-2.57, p = 0.037).
Conclusions: Endothelial dysfunction is associated with clopidogrel
response variability in patients after PCI receiving dual antiplatelet
therapy. These findings shed some light on the mechanisms affecting
individual platelet response to antiplatelet therapy and may explain the
non-straight forward association between clopidogrel dose, platelet
inhibition and cardiovascular outcome. (C) 2015 Elsevier Ireland Ltd.
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