An effective and rapid determination by MALDI/TOF/TOF of methionine sulphoxide content of ApoA‐I in type 2 diabetic patients

Increased oxidation of low density lipoprotein (LDL) is characteristic of atherosclerosis. In this frame, high density lipoproteins (HDL) play an important role, being able to remove lipid peroxides (LPOs) and cholesterol from oxidized LDL, so exhibiting a protective role against atherosclerosis. A wide range of reactive compounds lead to the oxidation of methionine (Met) residues with the formation of methionine sulphoxide (MetO) in apolipoprotein A‐I (ApoA‐I). Consequently, the determination of MetO level can give both an evaluation of oxidative stress and the reduced capability of ApoA‐I in LPOs and cholesterol transport. For these reasons, the development of analytical methods able to determine the MetO level is surely of interest, and we report here the results obtained by MALDI mass spectrometry. Copyright © 2013 John Wiley & Sons, Ltd.     

Anti-atherosclerotic activity of Betulinic acid loaded polyvinyl alcohol/methylacrylate grafted Lignin polymer in high fat diet induced atherosclerosis model rats

Betulinic acid is one such natural pentacyclic triterpenoid compound, holding various pharmacological properties but its poor bioavailability is the only limitation. One of the biological macromolecules such as Lignin is a plant-derived aromatic, eco-friendly and low-cost polymer that certainly self-assembles into nano-sized colloids. Therefore, onto the current investigation, we increased the bioavailability of betulinic acid by coating on to a nanopolymer prepared with poly vinyl alcohol, lignins and methyl acrylate. Betulinic acid loaded polyvinyl alcohol/ethylacrylate grafted Lignin polymer (PVA/Lig-g-MA) nanoformulation was characterized using FTIR, XRD, SEM and TEM analysis and also the drug entrapment, in vitro drug releasing capacity was done to examine the efficiency of the nanoformulation of a drug. The MTT assay was evaluated the cytotoxicity of synthesized nanoformulation against normal endothelial cells HUVEC and HAPEC to confirm the side effects of the drug. The anti-atherosclerotic property of the nanoformulation was ascertained in both in vitro condition (with HUVEC and HPAEC) and in vivo studies (with Wistar rats). As a result, the characterization studies and in vitro studies clearly confirmed the Betulinic acid loaded PVA/Lig-g-MA nanoformulation is an ideal nanopolymer and it doesn’t cause any cytotoxic effect in normal endothelial cells. It also decreased the lipopolysaccharides induced inflammation through the down-regulation of NFκB and MAP/JNK signaling molecule expressions. Following in vivo results confirmed the synthesized nanoformulation effectively decreased the hyperchlostremia, inflammation and vasoconstriction, which induced over high fat diet. The results of histopathological analysis of cardiac tissues also confirmed the cardioprotective role of synthesized nanoformulation. Overall, both the in vitro and in vivo studies authentically proven the Betulinic acid loaded PVA/Lig-g-MA nanoformulation would be a potent cost effective anti-atherosclerotic nanodrug.     

The Action of Peroxyl Radicals,Powerful Deleterious Reagents,Explains Why Neither Cholesterol Nor Saturated Fatty Acids Cause Atherogenesis and Age‐Related Diseases

Cells respond to alterations in their membrane structure by activating hydrolytic enzymes. Thus, polyunsaturated fatty acids (PUFAs) are liberated. Free PUFAs react with molecular oxygen to give lipid hydroperoxide molecules (LOOHs). In case of severe cell injury, this physiological reaction switches to the generation of lipid peroxide radicals (LOO^.). These radicals can attack nearly all biomolecules such as lipids, carbohydrates, proteins, nucleic acids and enzymes, impairing their biological functions. Identical cell responses are triggered by manipulation of food, for example, heating/grilling and particularly homogenization, representing cell injury. Cholesterol as well as diets rich in saturated fat have been postulated to accelerate the risk of atherosclerosis while food rich in unsaturated fatty acids has been claimed to lower this risk. However, the fact is that LOO^. radicals generated from PUFAs can oxidize cholesterol to toxic cholesterol oxides, simulating a reduction in cholesterol level. In this review it is shown how active LOO^. radicals interact with biomolecules at a speed transcending usual molecule–molecule reactions by several orders of magnitude. Here, it is explained how functional groups are fundamentally transformed by an attack of LOO^. with an obliteration of essential biomolecules leading to pathological conditions. A serious reconsideration of the health and diet guidelines is required.     

Study of the effect of atorvastatin on the interaction between ICAM-1 and CD11b by live-cell single-molecule force spectroscopy

The interaction between the cell adhesion molecule CD11b and its ligand ICAM-1 plays an important role in inflammatory responses in the disease of atherosclerosis. Atorvastatin is a commonly prescribed statin drug which has been considered as one of the most potent therapeutic agents for atherosclerosis due to its lipid-lowering effect. Recently, there is a growing body of evidence that atorvastatin has anti-inflammatory effect. We have applied the advanced method of live-cell single-molecule force spectros...     

Mathematical and physical modelling of the dynamic fluidic impedance of arteries using electrical impedance equivalents

In this work, a detailed mathematical and physical model for calculating the fluidic impedance of an artery is developed. Initially, the model calculates the impedance of a healthy artery, and then, it compares this with the alteration in the impedance of an artery with atherosclerosis. Copyright © 2013 John Wiley & Sons, Ltd.     

Transfer of pyrene-dietherphosphatidylcholine to serum lipoproteins

The nonhydrolyzable fluorescent diether analog of phosphatidylcholine, 1-O-hexadecyl-2-0-pyrenedecyl-sn-glycero-3-phosphocholine, has been synthesized as a stable probe for the determination of phospholipid transfer to different lipoprotein classes with potential phospholipase activities. After incubation of total human serum with the new probe at 37°C for 3 hours a characteristic partition equilibrium between the main lipoprotein fractions was observed. The fluorescent lipid was not degraded under these conditions and, therefore, served as a marker for choline glycerophospholipid distribution between and transport to serum lipoproteins.     

Surface‐Functionalized Nanoparticles by Olefin Metathesis: A Chemoselective Approach for In Vivo Characterization of Atherosclerosis Plaque

The use of click chemistry reactions for the functionalization of nanoparticles is particularly useful to modify the surface in a well‐defined manner and to enhance the targeting properties, thus facilitating clinical translation. Here it is demonstrated that olefin metathesis can be used for the chemoselective functionalization of iron oxide nanoparticles with three different examples. This approach enables, in one step, the synthesis and functionalization of different water‐stable magnetite‐based particles from oleic acid‐coated counterparts. The surface of the nanoparticles was completely characterized showing how the metathesis approach introduces a large number of hydrophilic molecules on their coating layer. As an example of the possible applications of these new nanocomposites, a focus was taken on atherosclerosis plaques. It is also demonstrated how the in vitro properties of one of the probes, particularly its Ca²⁺‐binding properties, mediate their final in vivo use; that is, the selective accumulation in atherosclerotic plaques. This opens promising new applications to detect possible microcalcifications associated with plaque vulnerability. The accumulation of the new imaging tracers is demonstrated by in vivo magnetic resonance imaging of carotids and aorta in the ApoE^?/? mouse model and the results were confirmed by histology.     

血流动力学与动脉粥样硬化

动脉粥样硬化引发的心血管疾病已成为疾病死亡的主要原因，动脉粥样硬化虽是一多因素疾病，但该疾病的局部性现象却与心血管系统的血流动力学特性有关。目前，人们在这一领域的研究重点主要集中于弄明局部应力，特别是流动剪切应力变化对动脉血管生理和病理的影响，本在综述血流动力学因素对动脉粥样硬化的影响的同时，根据实验研究提出了一些新的见解，认为血管内壁脂质浓度极化也是造成动脉粥样硬化的重要因素。     

Potential Role of Melatonin as an Adjuvant for Atherosclerotic Carotid Arterial Stenosis

Carotid artery stenosis (CAS) is an atherosclerotic disease characterized by a narrowing of the artery lumen and a high risk of ischemic stroke. Risk factors of atherosclerosis, including smoking, hypertension, hyperglycemia, hyperlipidemia, aging, and disrupted circadian rhythm, may potentiate atherosclerosis in the carotid artery and further reduce the arterial lumen. Ischemic stroke due to severe CAS and cerebral ischemic/reperfusion (I/R) injury after the revascularization of CAS also adversely affect clinical outcomes. Melatonin is a pluripotent agent with potent anti-inflammatory, anti-oxidative, and neuroprotective properties. Although there is a shortage of direct clinical evidence demonstrating the benefits of melatonin in CAS patients, previous studies have shown that melatonin may be beneficial for patients with CAS in terms of reducing endothelial damage, stabilizing arterial plaque, mitigating the harm from CAS-related ischemic stroke and cerebral I/R injury, and alleviating the adverse effects of the related risk factors. Additional pre-clinical and clinical are required to confirm this speculation.