Hardening Of Arteries Research Articles

Novel Peripheral Perfusion Dynamics Indices for Detecting and Grading Arterial Stenosis.

Peripheral artery disease causes severe morbidity, especially in diabetics and the elderly. There is a need for accurate noninvasive detection of peripheral arterial stenosis. The study has tested the hypothesis that arterial stenosis and the associated adaptation of the downstream circulation yield characteristic changes in the leg perfusion dynamics that enable early diagnosis, utilizing impedance plethysmography. The arterial perfusion dynamic was derived from impedance plethysmography (IPG). Two degrees of arterial stenosis were emulated by inflating a blood-pressure cuff around the thigh to 45 and 90mmHg, in healthy volunteers (n = 30). IPG signals were acquired continuously throughout the experiment. Ankle and brachial blood pressures were measured at the beginning of each experiment and at the end of each emulated stenosis phase. Thigh compressions did not affect the pulse-transit time, but prolonged the time to the peak perfusion wave. Segmentation of the perfusion upstroke into two phases, at the time point of maximum acceleration (MAT), revealed that arterial compression prolonged only the initial slow phase duration (SPd). The MAT and SPd were proportional to the emulated stenosis severity and detected the arterial stenosis with high sensitivity (>93%) and specificity (100%). The SPd increased from 46.4 ± 21.2ms at baseline to 75.4 ± 38.5ms and 145 ± 39ms under 45mmHg and 90mmHg compressions (p < 0.001), without affecting the pulse-transit time. The novel method and indices can identify and grade the emulated arterial stenosis with high accuracy and may assist in differentiating between focal arterial stenosis and widespread arterial hardening.

Nanotechnology-Based Strategies for Extended-Release Delivery of Angiotensin Receptor Blockers (ARBs): A Comprehensive Review.

There has been a significant shift in the perception of hypertension as an important contributor to the global disease burden. Approximately 6 % and 8 % of pregnancies are affected by hypertension, which can adversely affect the mother and the fetus. Furthermore, a hypertensive individual is at increased risk of developing kidney disease, arterial hardening, eye damage, and strokes. Using angiotensin receptor blockers (ARBs) is widespread in treating hypertension, heart failure, coronary artery disease, and diabetic nephropathy. Despite this, some ARBs have limited use due to their poor oral bioavailability and water solubility. To tackle this, a variety of nanoparticle (NP)-based systems, such as polymeric NPs (i. e., dendrimers), polymeric micelles, polymer-drug conjugates, lipid NPs, nanoemulsions, self-emulsifying drug delivery systems (SEDDS), solid lipid NPs (SLNs), nanostructured lipid carriers (NLCs), carbon-based nanocarriers, inorganic NPs, and nanocrystals, have been recently developed for efficient delivery of losartan, Valsartan (Val), Olmesartan (OLM), Telmisartan (TEL), Candesartan, Eprosartan, Irbesartan, and Azilsartan to target cells. This review article provides a literature-based comparison of the various classes of ARBs, their mechanisms of action, and an overview of the nanoformulations developed for ARB delivery and successfully applied to managing hypertension, diabetic complications, and other conditions.

Assessment of Remnant Lipoprotein Cholesterol and Oxidized Low density Lipoprotein Associated with Low-grade Inflammation in Coronary Heart Disease Subjects of Young South Indian Population.

Coronary heart disease (CHD) is a major disease entity responsible for significant mortality and morbidity in the Indian population. The prevalence of CHD is increasing day by day in India. The hardening of arteries is linked to oxidative variations in low-density lipoproteins (LDLs). Modification of LDL to oxidized LDL (ox-LDL) is a crucial step in the oxidation hypothesis of atherogenesis. Oxidized LDL and remnant lipoprotein cholesterol (RLP-C) stimulate the immune and inflammatory reactions and promote atherosclerosis. Because of its lesser size along with high cholesterol content, and increased residence period in blood the remnant lipoproteins are highly atherogenic. Remnant lipoproteins transport more cholesterol to macrophages compared to LDL particles. Remnant lipoproteins enter into the arterial wall easily and are taken up directly by macrophages. This leads to the formation of foam cells, thus initiating the lipid-laden plaque. High sensitive C-reactive protein acts as a nonspecific inflammatory marker. Oxidized LDL along with RLP-C and high-sensitivity C-reactive protein (hs-CRP) play crucial role in progression of CHD. The aim of the study is to assess ox-LDL and RLP-C associated with hs-CRP as potential biomarkers in the development of CHD. This cross-sectional study was conducted in Sri Ramaswamy Memorial Medical College Hospital and Research Centre on subjects appearing for master health check-up and medicine. This cross-sectional study was conducted on 273 subjects who were age and sex match in the age group of ≤45 years. 91 Non-Diabetic subjects with CHD, 91 Diabetic subjects with CHD, and 91 normal healthy subjects were selected as control. After overnight fasting, body fluid samples were collected for analysis for lipid profile, ox-LDL, and hs-CRP. Oxidized LDL and hs-CRP were measured by enzyme-linked immunosorbent assay (ELISA) method and lipid profile was measured using Auto Analyser AU480. Statistical analysis was done using Student's t-test and Pearson's correlation analysis for the comparison between two groups. The mean level of ox-LDL, RLP-C, and hs-CRP was significantly elevated in CHD group. A significantly positive correlation was observed between plasma ox-LDL, RLP-C, and hs-CRP. These results suggest that the link between high ox-LDL, RLP-C, and hs-CRP levels might be interrelated to atherogenesis in subjects with CHD. In addition to conventional parameters, ox-LDL, RLP-C, and hs-CRP can prove to be a valuable tool in risk assessment of CHD. Journal of the Association of Physicians of India (2022): 10.5005/japi-11001-0009.

The Temporal Pattern of Arterial Stiffness during Aging: A Large-Scale Cross-Sectional Study.

Brachial-ankle pulse wave velocity (baPWV) is a noninvasive clinical test that provides quantification for the stiffness of both the aorta and peripheral arteries by measuring the brachial and tibial arterial wave velocities. The temporal pattern of baPWV values during aging was investigated in this paper. A gradual increase in baPWV with respect to age was observed, suggesting an increase in the stiffness of arterial vessels as age increases. The ΔbaPWV value, defined as the absolute value of the difference between bilateral baPWV, also showed a positive correlation with aging. Many underlying physiological conditions such as hyperlipidemia, hypertension, diabetes, and hyperglycemia have previously been shown to elevate baPWV and contribute to the decline of arterial function. The effect of factors including biological sex, blood pressure, and blood glucose levels on the baPWV temporal pattern were also investigated. Between the ages of 18 and 50, men in the study had significantly higher baPWV readings than females of comparable age on average. However, after the age of 50, mean baPWV values increased at a greater rate in females than in males. In addition, blood pressure and blood glucose were shown to be associated with baPWV values. The results will improve existing prediction models for future cardiovascular episodes induced by arterial hardening in different age groups.

Comparative evaluation of color Doppler and conventional digital subtraction angiography in arterial disease

Introduction: Peripheral Arterial Occlusive Disease (PAOD) leads to narrowing and hardening of arteries which leads to increased risk of lower extremity amputation. Hence, the accuracy of non-invasive diagnostic methods such as Color Doppler (CD) needs to be assessed in comparison to the conventional digital subtraction angiography (CDSA). Objective: To compare color Doppler and conventional digital subtraction arteriography in patients of infragenicular arterial disease. To evaluate and correlate the findings of CD with arteriography as the gold standard, in PAOD of the lower extremities in supra-genicular part and to define whether color Doppler, is an alternative or an adjunct to DSA. Methods: In this study 60 patients suspected of lower limb PAD aged between 40 and 70 years were included. All these patients with symptoms suggestive of PAOD underwent color Doppler study of lower limb arterial system. Afterward, 55 patients of PAOD formed the subjects and their affected lower limbs evaluated by CD and arteriography, for localization and grading of lesion in the arteries, into normal/insignificant stenosis and occlusion. The sensitivity, specificity, and positive and negative predictive values of CD as compared to CDSA in arterial disease were calculated. Results were analyzed by two way contingency tables, using calculator, and SSP software. Results: As compared to conventional digital subtraction angiography, Doppler assessment was more sensitive specific with greater diagnostic accuracy. Conclusion: CD is better than conventional digital subtraction angiography in diagnosis of Grade 1 &2 cases, with better assessment of soft plaques, segmental flow and recanalization in PAD and CD performed well compared with conventional digital subtraction angiography. Hence color Doppler can be an alternative to conventional digital subtraction angiography in diagnosing peripheral arterial occlusive diseases in supragenicular part of lower limb arteries.

Mechanism involved in the Circulation of oxidized LDL and its Ratio; An Early Risk Marker in Diabetic and Non-Diabetic Subjects with Coronary Heart Disease

Under oxidative stress hardening of arteries is linked to oxidative variations in low density lipoproteins and imaginably more than one mechanism is involved in the atherosclerosis, where LDL is oxidized in all the cells of intimal wall during the progression of CHD. Ox-LDL act as a prognosticator of dysfunction in endothelium along with pro-thrombotic, pro-apoptotic, pro-inflammatory properties in subjects suffering from oxidative stress. Circulating ox-LDL is associated with the development of atherosclerosis but also numerous degenerative and age related disease. The objective of our study is to assess the levels of circulating oxidized LDL and its ratio in Diabetic and Non-Diabetic Subjects with CHD. This cross-sectional study was conducted in Department of General Medicine and Master Health check-up OP of SRM Medical College and Research Centre, Tamil Nadu, India. Totally 273 subjects in that 91 CHD patient without Diabetes, 91 CHD patient with diabetes and 91 healthy control in age group of 30 to 55 years and were age and sex matched. After overnight fasting blood samples were collected for analysis. ox-LDL were measured by ELISA method and Lipid Profile is measured using Auto Analyser AU480. Statistical analysis was done using student ‘t’ test and Pearson correlation analysis for the comparison between two groups. When compared to controls the mean level Low Density Lipoprotein and Plasma Oxidized LDL was significantly elevated in CHD group. Significantly positive correlation was observed between plasma oxidized LDL an LDL. The study concludes that increased circulating ox-LDL and its ratio are early risk marker and useful predictor of mortality in patients with CHD.For the diagnosis and treatment of coronary heart disease an appropriate method that reveal the mechanisms which increase circulating LDL and ox-LDL is needed.

Mechanisms of the Osteogenic Switch of Smooth Muscle Cells in Vascular Calcification: WNT Signaling, BMPs, Mechanotransduction, and EndMT.

Characterized by the hardening of arteries, vascular calcification is the deposition of hydroxyapatite crystals in the arterial tissue. Calcification is now understood to be a cell-regulated process involving the phenotypic transition of vascular smooth muscle cells into osteoblast-like cells. There are various pathways of initiation and mechanisms behind vascular calcification, but this literature review highlights the wingless-related integration site (WNT) pathway, along with bone morphogenic proteins (BMPs) and mechanical strain. The process mirrors that of bone formation and remodeling, as an increase in mechanical stress causes osteogenesis. Observing the similarities between the two may aid in the development of a deeper understanding of calcification. Both are thought to be regulated by the WNT signaling cascade and bone morphogenetic protein signaling and can also be activated in response to stress. In a pro-calcific environment, integrins and cadherins of vascular smooth muscle cells respond to a mechanical stimulus, activating cellular signaling pathways, ultimately resulting in gene regulation that promotes calcification of the vascular extracellular matrix (ECM). The endothelium is also thought to contribute to vascular calcification via endothelial to mesenchymal transition, creating greater cell plasticity. Each of these factors contributes to calcification, leading to increased cardiovascular mortality in patients, especially those suffering from other conditions, such as diabetes and kidney failure. Developing a better understanding of the mechanisms behind calcification may lead to the development of a potential treatment in the future.

Diagnostic Accuracy of Color Doppler and Calcium Scoring versus Dual-Energy Computed Tomography Angiography in the Assessment of Peripheral Arterial Diseases of Lower Limb.

Objectives:Peripheral arterial disease (PAD) leads to narrowing and hardening of arteries which leads to increased risk of lower extremity amputation. Hence, the accuracy of non-invasive diagnostic methods such as calcium scoring and color Doppler needs to be assessed in comparison to the gold standard dual-energy computed tomography (DECT) angiography. This study aims to evaluate the accuracy of color Doppler and calcium scoring when compared to DECT angiography in the assessment of PAD of the lower limb. It is a cross- sectional retrospective study.Material and Methods:The study included 55 patients aged between 40 and 70 years. All the patients with symptoms suggestive of PAD underwent color Doppler study of lower limb arterial system. Afterward, the patient underwent CT angiography. The first plain images were taken for calcium scoring following which contrast was given and further images were taken.Results:As compared to CT angiography assessment, Doppler assessment was 88.1% sensitive but only 69.2% specific with diagnostic accuracy of 83.6%. For angiographically detected atheromatous changes, color Doppler had sensitivity and specificity of 86.2% and 76.9%. The derived cutoff value >149.1 of calcium score in lower limb arteries was in 100% agreement with CT angiography detected PAD, whereas, for atheromatous changes, total calcium score at a cutoff value of >842.2 had sensitivity and specificity of 75.9% and 80.8%.Conclusion:Calcium scoring as compared to color Doppler has a higher diagnostic efficacy for the detection of DECT angiography confirmed PAD, whereas calcium score lacks adequate sensitivity at projected cutoff in the evaluation of atheromatous changes.

Intracranial and Extracranial Atherosclerosis: More Similar Than Different?

Atherosclerosis involves gradual arterial hardening secondary to the building up of lipid-laden plaques in the vessel wall, which may cause vascular stenosis, thromboembolism, or overgrowth across perforator arterial ostia.[1][1],[2][2] Despite common vascular risk factors and overlapping

Study of common carotid and brachial artery hemodynamic variations in periodontal disease in Central India-a clinical study

Background and aimThe linkage between periodontal and systemic diseases although well researched in the scientific area is not universally cognizant among the clinicians. It is critical to bring about the awareness of this inter-relationship as oral health is suggestive of systemic health. The aim of this study was a thorough hemodynamic assessment in patients having periodontal disease. Settings and designThis is an observational cross sectional study. The patients were selected from Outpatient Department of Cardiology and Periodontology in a tertiary care hospital in urban setting in Nagpur, India. MethodsThe study was conducted on 45 patients aged between 35 and 65 years. Echo-Doppler examination for internal diameter (ID), intima-media thickness (IMT) and blood flow velocity (PSV) measurements was executed in the right and left common carotid artery (CCA) and brachial artery (BA). Periodontal disease status was determined using parameters like Gingival Index, Plaque Index, probing pocket depth (PPD) and clinical attachment level (CAL). Statistical analysisDue to multiple comparison groups one-way Analysis of variance (ANOVA) with Bonferroni multiple comparison tests have been performed to conduct all possible pair-wise comparisons of means. ResultsThe present study showed that Carotid IMT and ID were high in the patients having cardiovascular disease (CVD) and periodontitis as compared to CVD alone, showing the additional effect caused by the presence of periodontal disease. ConclusionThe study findings support the proposition that periodontal disease may be associated with endothelial dysfunction which leads to atherosclerosis or hardening of arteries indicating increased cardiovascular risk.

Risk of hypertension after hysterectomy: a population-based study.

Hysterectomy is the second most common surgery performed mainly for benign uterine pathologies in females. The association between hysterectomy and the subsequent risk of hypertension remains controversial. This study investigated the risk of developing hypertension in women who had a hysterectomy. Population-based retrospective cohort study. We used the Taiwan National Health Insurance Research Database with claims data of 1 million randomly selected insured individuals. Women with and without hysterectomy and bilateral salpingo-oophorectomy, aged 30-49years, were identified in 2000-2013 from the insurance data. From the claims data, we identified 6674 women with hysterectomy without hypertension at the time of the surgery. The comparison cohort were 26696 women randomly selected from women without hysterectomy and hypertension, matched by age and the year hysterectomy was performed. Adjusted hazard ratio (aHR) of hypertension was estimated after controlling for comorbidities. Prediction for hypertension following hysterectomy for benign disease. Both cohorts had a median age of 43.9years. After a median follow up of 6.4years, the incident hypertension was higher in the hysterectomy cohort than in the comparison cohort, with an adjusted hazard ratio (aHR) of 1.35 [95% confidence interval (CI)1.27-1.44]. The incidence increased with age, with a higher aHR in hysterectomised women aged 40-49years (aHR1.37, 95% CI1.06-1.83) than in those aged 30-39years (aHR 1.22, 95% CI1.02-1.46). Findings in this study suggest that women with hysterectomy are more likely to be diagnosed with hypertension in the follow-up period. Women with hysterectomy before 50years of age are at an increased risk of developing subsequent hypertension. Hysterectomy is one of the most common surgeries for women with benign uterine disease. Hysterectomy may lead to a sudden decline in the production of sex hormone (estrogen and progesterone), which is responsible for vessel wall endothelial dysfunction leading to hardening of arteries and subsequent hypertension. However, the association between hysterectomy and risk of hypertension remains controversial. This study investigated whether premenopausal women have an elevated risk of hypertension after hysterectomy. This study employed the Taiwan National Health Insurance Research Database to identify 6674 women 30-49 years old who had a hysterectomy between 2000 and 2013, and a comparison group of 26696 women who did not have a hysterectomy matched by age. Women in both the groups had no hypertension at baseline (recruiting date or within 1 year after recruiting date). By the end of 2013, we found that 1196 (17.9%) and 3613 (13.5%) women had developed hypertension in the hysterectomy and the comparison groups, respectively. The hypertension incidence was 1.4-fold greater in the hysterectomy group than in the control group (27.8 versus 20.2/1000 person-years).

A new era for dementia epidemiology: Alzheimer's disease, hardening of arteries, or just old age?

A new era for dementia epidemiology: Alzheimer's disease, hardening of arteries, or just old age?

A Review of Pediatric Cardiovascular Risk Factors and Current Guidelines

Dyslipidemia is a highly prevalent condition, and includes a collection of diseases that cause increased levels of plasma triglycerides and/or cholestrol, or decreased levels of HDL-C, with a prototypical disease being familial hypercholesterolemia. Dyslipidemic conditions promote increased atherogenesis through the oxidation of lipids by macrophages, and an increased response to injury by the vascular endothelium. This vascular damage, loss of vascular compliance, and overall hardening of arteries lead to sequellae such as cardiovascular disease, cerebrovascular events, and aneurysm formation. It has been established that certain risk factors predispose individuals to the sequellae of atherosclerosis, including smoking, diabetes, hypertension, and hyperlipidemia. However, studies show that these risk factors can be seen in children as well. This review aims to assess the effect of these risk factors and demonstrate their effects through adolescence into adulthood.

Eating the Dead to Keep Atherosclerosis at Bay.

Atherosclerosis is the primary cause of coronary heart disease (CHD), ischemic stroke, and peripheral arterial disease. Despite effective lipid-lowering therapies and prevention programs, atherosclerosis is still the leading cause of mortality in the United States. Moreover, the prevalence of CHD in developing countries worldwide is rapidly increasing at a rate expected to overtake those of cancer and diabetes. Prominent risk factors include the hardening of arteries and high levels of cholesterol, which lead to the initiation and progression of atherosclerosis. However, cell death and efferocytosis are critical components of both atherosclerotic plaque progression and regression, yet, few currently available therapies focus on these processes. Thus, understanding the causes of cell death within the atherosclerotic plaque, the consequences of cell death, and the mechanisms of apoptotic cell clearance may enable the development of new therapies to treat cardiovascular disease. Here, we review how endoplasmic reticulum stress and cholesterol metabolism lead to cell death and inflammation, how dying cells affect plaque progression, and how autophagy and the clearance of dead cells ameliorates the inflammatory environment of the plaque. In addition, we review current research aimed at alleviating these processes and specifically targeting therapeutics to the site of the plaque.

A Simple Way for the Preparation of Natural Antioxidant Quercetin from Rutin by Subcritical Water.

Context:Quercetin (QR) is a natural strong antioxidant of the plant origins. It is used for treating conditions of heart and blood vessels including “hardening of arteries” (atherosclerosis), high cholesterol, heart disease, circulation problems, preventing cancer, for treating chronic infections of the prostate, etc.,Aims:The aim of this work was to development and study of an acid-free technique for the preparation of QR from rutin (RT) that requires no use of acids and toxic organic solvents.Materials and Methods:For the first time, the subcritical water that serves as a reactant and a solvent were used to obtain QR in good yields starting from RT. High-performance liquid chromatography combined with mass spectrometry was used to determine the quantitative and qualitative compositions of the obtained products.Conclusions:For the first time, a new acid-free technique was used for the synthesis of natural antioxidant QR from an RT by subcritical water. That way requires no use of acids and/or toxic organic solvents. It has been shown that variation of only one parameter of the process (temperature of subcritical water) allows alteration to the composition of the hydrolysis products. The new method developed for the production of QR in subcritical water is environmentally friendly and faster than conventional hydrolysis methods that use acidic or enzymatic hydrolysis. The proposed technique has a potential for the future development of inexpensive and environmentally friendly technologies for the production of new pharmaceutical plant-based substances.

A Review on Atherosclerotic Biology, Wall Stiffness, Physics of Elasticity, and Its Ultrasound-Based Measurement.

Functional and structural changes in the common carotid artery are biomarkers for cardiovascular risk. Current methods for measuring functional changes include pulse wave velocity, compliance, distensibility, strain, stress, stiffness, and elasticity derived from arterial waveforms. The review is focused on the ultrasound-based carotid artery elasticity and stiffness measurements covering the physics of elasticity and linking it to biological evolution of arterial stiffness. The paper also presents evolution of plaque with a focus on the pathophysiologic cascade leading to arterial hardening. Using the concept of strain, and image-based elasticity, the paper then reviews the lumen diameter and carotid intima-media thickness measurements in combined temporal and spatial domains. Finally, the review presents the factors which influence the understanding of atherosclerotic disease formation and cardiovascular risk including arterial stiffness, tissue morphological characteristics, and image-based elasticity measurement.

Design and Development of Novel Synergistic Formulation of Pravastatin and Aspirin for the Treatment of Atherosclerosis and its Evaluation

Coronary artery diseases (CAD) represent a condition in which the blood supply to the heart muscle is partially or completely blocked. In atherosclerosis, the hardening of arteries occurs with decreasing elasticity of the arteries. For management of disease, cholesterol lowering agents like Pravastatin and anti-platelet agent like aspirin are commonly used. Various studies have shown that these agents when given in combination results in synergistic pharmacological activity, however they are not chemically compatible. In present work, formulation approaches utilizes principles of pelletization and coating technologies to form a stable drug delivery system. The enteric coating of the core aspirin pellets was done using Eudragit L 100 (6%) with polyethylene glycol 6000 (0.6%) till 2.5, 5 and 7.5% weight gain was obtained. A barrier coating on enteric coated pellets was applied using hydroxyl propyl methyl cellulose (HPMC) 15 cps solution. For the layering of Pravastatin over the barrier coated pellets, Pravastatin was dispersed in 2.5% HPMC solution. The coating solution was sprayed over the pellets till a dose strength equivalent to 10 mg of Pravastatin per 250 mg of pellets was obtained. The optimized pellets were subjected to evaluation of drug content, bulk density, crushing strength, friability, size distribution, packing ability and in-vitro drug release, stability studies and in-vivo performance using trition X 100 induce hyperlipidaemia rat model. The developed formulation showed an effective cholesterol lowering effect as compared to standard marked formulation of Pravastatin. It indicates the development of stable combination formulation in which aspirin forms the enteric coated sustained release core and that of Pravastatin fast releasing outer layers of the pellets.

Arterial Stiffness: A Novel Cardiovascular Risk Factor in Kidney Disease Patients

Prospective observational studies have shown that arterial stiffness is a strong and independent predictor of cardiovascular disease in hemodialysis patients. Recent evidence further supports that arterial hardening predicts cardiovascular and all-cause mortality in peritoneal dialysis patients, renal transplant recipients and patients with chronic kidney disease (CKD) not on dialysis. Of note, dissociation of arterial stiffness with blood pressure reduction were related to worsened cardiovascular outcome in kidney disease patients, suggesting that arterial stiffness may not only be a predictor, but also a true risk factor, representing a specific and potentially reversible pattern of outward arterial remodeling in these individuals. On this basis, arterial stiffness has emerged as a novel therapeutic target for cardiovascular risk reduction in patients with CKD; specific interventions, such as renin-angiotensin-system blockade, use of statins, and decrease of calcium- phosphate product may delay the progression of arteriosclerotic process. This article summarizes the accumulated evidence from clinical and epidemiological studies regarding the prognostic significance of arterial stiffening on cardiovascular outcomes and provides insights on possible treatment strategies for arterial stiffness attenuation in patients with CKD.

Abstract 19822: Arterial Calcification Can Be Inhibited via Stress Protein Induction Through a PPAR-dependent Pathway

Introduction: Cardiovascular disease occurs prematurely in chronic inflammatory conditions such as Chronic Kidney Disease (CKD) and unfortunately, remains the leading cause of death in these patients. Vascular calcification (VC) is a significant contributor to cardiovascular mortality in CKD patients with the sequela of arterial hardening, congestive heart failure and sudden cardiac death. We recently reported that heat shock protein 72 (HSP72) when inducted, can inhibit the development of VC. Hypothesis: We hypothesize that HSP72 exerts its vasculo-protective effects by functioning as a molecular chaperon for peroxisome proliferator-activated receptor γ (PPARγ). Methods: We developed an in vitro long-term calcification model using HA-SMCs treated with calcification medium (CM) containing 5mM CaCl2 and 5mM β-glycerophosphate for 21 days. Cells were subjected to heat shock treatment at 43°C for 30 minutes daily to induce HSP72. Calcification was assessed qualitatively by alizarin red staining and quantitatively by the arsenazo III method. Results: Our results show that inducible HSP72 is significantly expressed following heat shock treatment in HA-SMCs. Induction of HSP72 inhibited the development of VC in our long-term calcification model and these effects were abolished by HSP72 siRNA, in vitro. We next showed that HSP72 formed a protein-protein complex with PPARγ by co-immunoprecipitation. Expression of both these proteins was down-regulated in calcific HA-SMCs and their gene expression was down regulated in atherosclerotic human arteries. Furthermore, we found that the PPARγ inhibitor, FABP4 (fatty acid binding protein-4) which function as an atherosclerosis promoter was up-regulated in calcified human arteries. Lastly, induction of HSP72 restored expression of the HSP72-PPARγ complex and inhibited upregulation of FABP4 with reduction in calcification in our in vitro calcification model. These vasculo-protective effects were abolished by HSP72 siRNA. Conclusion: HSP72 is a powerful inhibitor of VC and exerts its vasculo-protective effects by functioning as a molecular chaperon to stabilize PPARγ and regulate the PPARγ-FABP4 pathway. We suggest treatment strategies involving induction of HSP72 as a new approach to inhibit VC.

Optimal Feature Selection for Carotid Artery Image Segmentation Using Evolutionary Computation

Atherosclerosis is hardening of arteries due to high blood pressure and high cholesterol. It causes heart attacks, stroke and peripheral vascular disease and is the major cause of death. In this paper we have attempted a method to identify the presence of plaque in carotid artery from ultrasound images. The ultrasound image is segmented using improved spatial Fuzzy c means algorithm to identify the presence of plaque in carotid artery. Spatial wavelet, Hilbert Huang Transform (HHT), Moment of Gray Level Histogram (MGLH) and Gray Level Co-occurrence Matrix (GLCM) features are extracted from ultrasound images and the feature set is reduced using genetic search process. The intima media thickness is measured using the proposed method. The IMT values are measured from the segmented image and trained using MLBPNN neural network. The neural network classifies the images into normal and abnormal.