Significant Plaque Regression Research Articles

Hyaluronic Acid-Guided Cerasome Nano-Agents for Simultaneous Imaging and Treatment of Advanced Atherosclerosis.

Early noninvasive screening and regression therapy for vulnerable atherosclerotic plaques remain challenging. In this study, it is aimed to develop a new approach for the active targeting of atherosclerotic plaques with nano-agents to aid imaging and treatment. Biocompatible hyaluronic acid (HA)-guided cerasomes are generated to selectively target CD44-positive cells within the plaque in in vitro studies and in vivo testing in Apoe-/- mice. Rosuvastatin (RST) is encapsulated in the HA-guided cerasome nano-formulation to produce HA-CC-RST, which results in significant plaque regression as compared to treatment with the free drug. Moreover, gadodiamide-loaded HA-CC enhances magnetic resonance images of vulnerable plaques, thereby attaining the goal of improved simultaneous treatment and imaging. Transcriptomic analysis confirms plaque regression with HA-CC-RST treatment, which potentially benefits from the anti-inflammatory effect of RST. In summary, a safe and efficient nano-formulation for the targeted delivery of active agents to atherosclerotic plaques is developed and may be applicable to other diagnostic and therapeutic agents for atherosclerosis treatment.

Impact of early intervention with alogliptin on coronary plaque regression and stabilization in patients with acute coronary syndromes

Background and aimsAnti-atherosclerotic effects of early intervention with dipeptidyl peptidase-4 inhibitors remain poorly defined. MethodsIn a prospective, single-center, randomized trial, 66 patients with acute coronary syndrome (ACS) and mild dysglycemia (HbA1c 6.0 (5.7, 6.3)%, 58% of impaired glucose tolerance) were randomly assigned to receive alogliptin (n = 33) or placebo (n = 33) in addition to standard treatments. Serial intravascular ultrasound (IVUS) was performed at baseline and 10 months to evaluate changes in coronary percent plaque volumes (%PV) and plaque tissue components of non-culprit lesions (NCLs). ResultsBaseline clinical and IVUS characteristics, as well as decreases in HbA1c and lipid variables during 10 months, did not differ significantly between the 2 groups. In contrast, with respect to vascular responses, the alogliptin group showed significantly greater decreases in plaque volumes (−0.3 ± 0.6 vs. −0.04 ± 0.7 mm3/mm, p = 0.03) and %PV (−0.9 ± 2.8 vs. 1.2 ± 3.6%, p = 0.01), with a tendency toward smaller lumen loss (−0.1 ± 0.7 vs. −0.4 ± 0.8 mm3/mm, p = 0.07) compared with the placebo group. Significantly decreased percent necrotic volumes (%NV) (−1.9 ± 3.8 vs. 0.3 ± 3.7%, p = 0.03) and increased fibrotic volumes (2.5 ± 5.0 vs. −0.3 ± 5.3%, p = 0.05) were or tended to be seen in alogliptin versus placebo groups at 10 months. In multiple regression analysis, alogliptin use was a statistically significant determinant of changes in %PV (β = −0.33, p = 0.004) and %NV (β = −0.28, p = 0.03) at 10 months. ConclusionsAlogliptin treatment, independently of glycemic and lipid status, resulted in significant plaque regression and stabilization in NCLs in patients with ACS and mild dysglycemia, suggesting the potential utility of early intervention with incretin-based treatments for this patients’ subset.

In This Issue

HomeCirculation ResearchVol. 129, No. 5In This Issue Free AccessIn BriefPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessIn BriefPDF/EPUBIn This Issue Ruth Williams Ruth WilliamsRuth Williams Search for more papers by this author Originally published19 Aug 2021https://doi.org/10.1161/RES.0000000000000499Circulation Research. 2021;129:511is related toElectronic and Tobacco Cigarettes Alter Polyunsaturated Fatty Acids and Oxidative Biomarkersis related toGlucose Derivative Induced Vasculopathy in Children on Chronic Peritoneal DialysisSilencing Myeloid Netrin-1 Induces Inflammation Resolution and Plaque RegressionElectronic and Tobacco Cigarettes Alter Polyunsaturated Fatty Acids and Oxidative Biomarkers (p 514)Gupta et al measure oxidized lipid biomarkers to assess health risks of electronic cigarettes.E-cigarettes have surged in popularity in the last decade. While they are generally viewed as a safe alternative to smoking tobacco, studies suggest that E-cigarettes, like tobacco ones, cause oxidative stress, inflammation and endothelial dysfunction in users. Indeed, the aerosols produced during vaping contain comparable levels of reactive oxygen species (ROS) to those in tobacco smoke. Data on the extent to which E-cigarette ROS influence cardiovascular health is lacking, however. To address this, Gupta and colleagues recruited 32 chronic users of E-cigarettes, 29 chronic tobacco smokers, and 45 individuals that used neither, and measured their plasma levels of oxidative biomarkers. The team found similarities and differences between E-cigarette and tobacco users. Both, for example, had increased plasma antioxidant capacity and decreased levels of oxidized linoleic acid compared with the levels seen in non-users, while arachidonic acid levels were raised in tobacco smokers and reduced in the E-cigarette users. Overall, however, biomarker levels were deemed to be intermediate for E-cigarette users between non-users and tobacco users. The study suggests, therefore, that while E-cigarettes carry a lower health risk than tobacco ones, they are by no means safe.Download figureDownload PowerPointGlucose Derivative Induced Vasculopathy in Children on Chronic Peritoneal Dialysis (p e102)Glucose degradation products damage blood vessels during dialysis, report Bartosova et al.Diabetes, high blood pressure and obesity are risk factors for both cardiovascular disease (CVD) and chronic kidney disease (CKD). Worse still, loss of kidney function and even dialysis itself are thought to exacerbate cardiovascular issues. In the case of dialysis, it’s thought that high levels of glucose degradation products (GDPs) in the dialysis fluids can promote the addition of sugar moieties to vascular proteins and lipids (glycation), causing vessel damage. To investigate this theory, Bartosova and colleagues studied vascular tissue from children with CKD receiving dialysis fluid with either high levels or low levels of GDPs, or that were not on dialysis at all. Proteome and transcriptome analyses of the vessel tissues revealed that, compared with patients on no or low-GDP fluids, patients receiving high-GDP fluids had higher levels of damaging glycation, increased transcription of genes involved in cell death, and decreased transcription of genes involved in cell survival and cytoskeleton organization. In line with these findings, vessels from high-GDP patients displayed considerable evidence of damage (apoptosis, cytoskeletal disintergration, thickened intimas). The results thus confirm GDPs can cause vasculopathy and suggest low-GDP fluids should be favored for dialysis.Download figureDownload PowerPointTargeting Netrin-1 in Established Atherosclerosis Promotes Inflammation Resolution and Plaque Regression (p 530)Blocking netrin-1 diminishes atherosclerotic plaques in mice, say Schlegel et al.While excess lipids in the blood spur the development of atherosclerosis, the disease quickly becomes one of chronic inflammation that encourages the persistence of the lipid-filled plaques in vessel walls. Indeed, sustained inflammation is thought to explain why lipid-lowering drugs often aren’t enough to combat the condition. Inflammation-suppressing drugs are also being investigated, but because these may cause susceptibility to infections, Schlegel and colleagues reasoned that promoting resolution of inflammation may be a preferable goal. To that end, the team tested blocking nectrin-1 in atherosclerosis-prone mice. Originally identified as a factor essential for nerve cells, Netrin-1 has also been found in macrophages where it promotes persistence and survival of the cells in atherosclerotic plaques. The team showed that in mice with advanced atherosclerosis, turning off netrin-1 in macrophages—via an inducible genetic switch—led to significant plaque regression. Not only did plaque macrophages exhibit reduced retention, proliferation and survival, those that remained were more likely to be pro-resolving. While susceptibility to infection was not investigated in this study, the results suggest in principle that netrin-1 blockade could be a strategy for atherosclerosis treatment.Download figureDownload PowerPoint Previous Back to top Next FiguresReferencesRelatedDetailsRelated articlesElectronic and Tobacco Cigarettes Alter Polyunsaturated Fatty Acids and Oxidative BiomarkersRajat Gupta, et al. Circulation Research. 2021;129:514-526Glucose Derivative Induced Vasculopathy in Children on Chronic Peritoneal DialysisMaria Bartosova, et al. Circulation Research. 2021;129:e102-e118Silencing Myeloid Netrin-1 Induces Inflammation Resolution and Plaque RegressionMartin Schlegel, et al. Circulation Research. 2021;129:530-546 August 20, 2021Vol 129, Issue 5 Advertisement Article InformationMetrics © 2021 American Heart Association, Inc.https://doi.org/10.1161/RES.0000000000000499 Originally publishedAugust 19, 2021 PDF download Advertisement

The Role of Angiotensin Antagonism in Coronary Plaque Regression: Insights from the Glagovian Model.

The benefit of antagonizing the effect of the renin angiotensin aldosterone system (RAAS), notably by the use of angiotensin-converting enzyme inhibitor (ACEi) and angiotensin II type 1 receptor blocker (ARB) for coronary artery disease (CAD), has been demonstrated in multiple studies, which may be attributed to their ability to inhibit the deleterious effect of RAAS to the cardiovascular system. It is well known that angiotensin II (Ang II) plays a vital role in atheromatous plaque formation and progression through multiple pathways, including inflammatory and arterial remodeling aspects. Significant coronary atheromatous plaque regression has been previously demonstrated in various studies using statin agents. Similar results have been reported in different studies using angiotensin inhibitor agents, notably ARB agents. Analysis from various trials utilizing ARB showed a significant plaque regression using olmesartan and telmisartan as evaluated by IVUS studies. In contrary, the use of ACEi did not demonstrated significant plaque regression, which may be attributed to the heavy plaque calcification in respective studies. On this review, we aim to present the basic mechanism on the role of RAAS in plaque modulation and its arterial remodeling aspect, which is then integrated with the clinical evidence based on the available intravascular ultrasonography (IVUS) studies on coronary arteries.

Regression of human coronary artery plaque is associated with a high ratio of (18-hydroxy-eicosapentaenoic acid + resolvin E1) to leukotriene B4.

Inflammation in arterial walls leads to coronary artery disease (CAD). We previously reported that a high omega-3 fatty index was associated with prevention of progression of coronary atherosclerosis, a disease of chronic inflammation in the arterial wall. However, the mechanism of such benefit is unclear. The two main omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are precursors of specialized pro-resolving lipid mediators (SPMs)-resolvins and maresins-which actively resolve chronic inflammation. To explore whether SPMs are associated with coronary plaque progression, levels of SPMs and proinflammatory mediators (leukotriene B4 [LTB4 ] and prostaglandins) were measured using liquid chromatography-tandem mass spectrometry in 31 statin-treated patients with stable CAD randomized to either EPA and DHA, 3.36 g daily, or no EPA/DHA (control). Coronary plaque volume was measured by coronary computed tomographic angiography at baseline and at 30-month follow-up. Higher plasma levels of EPA+DHA were associated with significantly increased levels of two SPMs-resolvin E1 and maresin 1-and 18-hydroxy-eicosapentaenoic acid (HEPE), the precursor of resolvin E1. Those with low plasma EPA+DHA levels had a low (18-HEPE+resolvin E1)/LTB4 ratio and significant plaque progression. Those with high plasma EPA+DHA levels had either low (18-HEPE+resolvin E1)/LTB4 ratios with significant plaque progression or high (18-HEPE+resolvin E1)/LTB4 ratios with significant plaque regression. These findings suggest that an imbalance between pro-resolving and proinflammatory lipid mediators is associated with plaque progression and potentially mediates the beneficial effects of EPA and DHA in CAD patients.

Impact of serum lipoprotein (a) level on coronary plaque progression and cardiovascular events in statin-treated patients with acute coronary syndrome: a yokohama-acs substudy

BackgroundLipoprotein (a) [Lp(a)] has been reported to be a residual risk factor in patients who have achieved target lipid levels. The aim of the present study was to investigate the associations of Lp(a) with plaque progression and major cardiovascular events in patients with acute coronary syndromes (ACS). MethodsThe Yokohama-ACS study included 102 patients with ACS who underwent intravascular ultrasound (IVUS) at baseline and at 10-month follow-up after percutaneous coronary intervention (PCI). The patients were randomly assigned to receive either moderate- or low-intensity statin therapy. IVUS was performed to measure the plaque volume at non-culprit lesions. We enrolled 76 patients for whom Lp(a) levels at 10-month follow-up were available. ResultsThe patients were divided into 2 groups according whether their Lp(a) levels were ≤20 mg/dl [low Lp(a) group; n = 49] or >20 mg/dl [high Lp(a) group; n = 27]. Baseline characteristics and low-density lipoprotein cholesterol levels at 10-month follow-up were similar in the low Lp(a) group and high Lp(a) group (87 ± 29 mg/dl vs. 93 ± 27 mg/dl, p = 0.42). The low Lp(a) group had significant plaque regression, whereas the high Lp(a) group showed slight plaque progression (−6.8% vs. 2.5%, p = 0.02). Ninety-five percent of the prognostic data were obtained 5 years after PCI. The cumulative event-free survival rate was significantly lower in the high Lp(a) group (p = 0.02; log-rank test). ConclusionsLp(a) levels may be an alternative predictor of further plaque regression and the likelihood of major adverse cardiovascular events in statin-treated ACS patients.

Impact of Cilostazol on the Progression of Carotid Atherosclerosis in Patients with Retinal Vascular Occlusion

Cilostazol, a selective phosphodiesterase three inhibitor, has been proposed to have beneficial effects in the prevention of atherosclerosis. We aimed to investigate the effects of cilostazol on carotid intima-media thickening (IMT) and total plaque area (TPA) in patients with retinal vascular occlusion. A total of 63 consecutive vascular occlusive retinopathy patients with carotid atherosclerosis were enrolled. We examined changes in the carotid IMT/TPA and visual acuity/macular thickness before and after 1-year treatment with cilostazol (200mg/day). The mean IMT of both common carotid arteries (CCAs) and internal carotid arteries (ICAs) were significantly reduced after cilostazol treatment. There was no significant difference in the TPA of both CCAs before and after the treatment (before; 0.61±0.94 vs. after; 0.45±0.79cm(2) , P=0.291); however, significant plaque regression (before; 0.14±0.15 vs. after; 0.25±0.14 cm(2) , P=0.004) was observed in selected patients (n=30) with a TPA <0.5cm(2) . The improvement in macular thickness was significantly associated with an improvement in carotid IMT (r=0.42, P=0.001) and TPA (r=0.23, P=0.04). Cilostazol potently inhibited the progression of carotid IMT and may play a role in the early carotid plaque regression in patients with retinal vascular occlusion.

Elimination of macrophages drives LXR-induced regression both in initial and advanced stages of atherosclerotic lesion development

While numerous studies have aimed to develop strategies to inhibit the development and progression of atherosclerosis, recent attention has focussed on the regression of pre-existing atherosclerotic plaques. As important regulator of total body cholesterol homeostasis, the liver X receptor (LXR) could possibly be an important target to induce regression.Here, we describe the effect of LXR activation by the synthetic agonist T0901317 on lesion regression in different mouse models with early fatty streak lesions or advanced collagen-rich lesions. Although T0901317 caused a dramatic increase in plasma (V)LDL levels in low-density lipoprotein (LDL) receptor knockout mice, no further increase in lesion size was observed, which points to beneficial LXR activity in the vascular wall. In normolipidemic C57BL/6 mice with cholate diet-induced atherosclerotic lesions, T0901317 treatment improved plasma lipoprotein levels and induced lesion regression (−43%, p<0.05). Apolipoprotein E (APOE) reconstitution in APOE knockout mice by means of bone marrow transplantation dramatically improved plasma lipoprotein profiles and resulted in a marked regression of initial (−45%, p<0.001) and advanced lesions (−23%, p<0.01). Atherosclerosis regression was associated with a decrease in the absolute macrophage content (−84%, p<0.001). T0901317 supplementation further decreased the size of early (−71%, p<0.001 vs baseline; −48%, p<0.01 vs chow diet alone) and more advanced atherosclerotic lesions (−36%, p<0.001 and −17%, p=0.06 respectively).In conclusion, our study highlights the potential of LXR agonist T0901317 to stimulate removal of macrophages from atherosclerotic lesions ultimately leading to a highly significant plaque regression of both early and advanced atherosclerotic lesions.

Quoi de neuf en recherche dermatologique ?

Dermatological research is more and more productive and its level higher and higher. Choosing the most significant articles is difficult. Mast cell plays a role in the initiation of inflammation and therefore in poorer healing. Keratinocytes derive from stem cells and progenitors, which are independent. They can be activated directly by heat through sensory proteins at their surface. The cutaneous nervous system has an organization similar to that of the most complex sensory organs. In psoriasis, denervation induces a significant plaque regression. The cerebral integration of skin appearance modulates the skin reactivity to histamine. Pruritus is linked to specific receptors in the skin, which give specific projections into the brain and are histamine-dependent or not. Atopic dermatitis may be linked to the nonspecific activation of Th2 immune system, particularly to abnormalities of the skin barrier. Skin bacteria, but not intestinal, modulate the formation of skin immunity. Raf kinases are well known in melanoma and play an important role in physiological conditions: they are not essential to the initial development of the melanocyte lineage but to maintain it. In culture, melanocytes can be dedifferentiated in melanoblasts. Sunburns are consecutive to the activation of TLR3 by UVB. ANRIL gene is involved in the polymorphism of neurofibromatosis 1 and gene RAD51B is linked to the risk of male breast cancer. MCV infection is linked to sites with sialic acid. Aging objectified by telomere shortening is accelerated by stress.

High HbA1c levels correlate with reduced plaque regression during statin treatment in patients with stable coronary artery disease: Results of the coronary atherosclerosis study measuring effects of rosuvastatin using intravascular ultrasound in Japanese subjects (COSMOS)

BackgroundThe incidence of cardiac events is higher in patients with diabetes than in people without diabetes. The Coronary Atherosclerosis Study Measuring Effects of Rosuvastatin Using Intravascular Ultrasound in Japanese Subjects (COSMOS) demonstrated significant plaque regression in Japanese patients with chronic coronary disease after 76 weeks of rosuvastatin (2.5 mg once daily, up-titrated to a maximum of 20 mg/day to achieve LDL cholesterol <80 mg/dl).MethodsIn this subanalysis of COSMOS, we examined the association between HbA1c and plaque regression in 40 patients with HbA1c ≥6.5% (high group) and 86 patients with HbA1c <6.5% (low group).ResultsIn multivariate analyses, HbA1c and plaque volume at baseline were major determinants of plaque regression. LDL cholesterol decreased by 37% and 39% in the high and low groups, respectively, while HDL cholesterol increased by 16% and 22%, respectively. The reduction in plaque volume was significantly (p = 0.04) greater in the low group (from 71.0 ± 39.9 to 64.7 ± 34.7 mm3) than in the high group (from 74.3 ± 34.2 to 71.4 ± 32.3 mm3). Vessel volume increased in the high group but not in the low group (change from baseline: +4.2% vs −0.8%, p = 0.02). Change in plaque volume was significantly correlated with baseline HbA1c.ConclusionsDespite similar improvements in lipid levels, plaque regression was less pronounced in patients with high HbA1c levels compared with those with low levels. Tight glucose control during statin therapy may enhance plaque regression in patients with stable coronary disease.Trial registrationClinicalTrials.gov, Identifier NCT00329160

An Essential Role for Diet in Exercise-Mediated Protection against Dyslipidemia, Inflammation and Atherosclerosis in ApoE-/- Mice

BackgroundDiet and exercise promote cardiovascular health but their relative contributions to atherosclerosis are not fully known. The transition from a sedentary to active lifestyle requires increased caloric intake to achieve energy balance. Using atherosclerosis-prone ApoE-null mice we sought to determine whether the benefits of exercise for arterial disease are dependent on the food source of the additional calories.Methods and ResultsMice were fed a high-fat diet (HF) for 4.5 months to initiate atherosclerosis after which time half were continued on HF while the other half were switched to a high protein/fish oil diet (HP). Half of each group underwent voluntary running. Food intake, running distance, body weight, lipids, inflammation markers, and atherosclerotic plaque were quantified. Two-way ANOVA tests were used to assess differences and interactions between groups. Exercised mice ran approximately 6-km per day with no difference between groups. Both groups increased food intake during exercise and there was a significant main effect of exercise F((1,44) = 9.86, p<0.01) without interaction. Diet or exercise produced significant independent effects on body weight (diet: F(1,52) = 6.85, p = 0.012; exercise: F(1,52) = 9.52, p<0.01) with no significant interaction. The combination of HP diet and exercise produced a greater decrease in total cholesterol (F(1, 46) = 7.9, p<0.01) and LDL (F(1, 46) = 7.33, p<0.01) with a large effect on the size of the interaction. HP diet and exercise independently reduced TGL and VLDL (p<0.05 and 0.001 respectively). Interleukin 6 and C-reactive protein were highest in the HF-sedentary group and were significantly reduced by exercise only in this group. Plaque accumulation in the aortic arch, a marker of cardiovascular events was reduced by the HP diet and the effect was significantly potentiated by exercise only in this group resulting in significant plaque regression (F1, 49 = 4.77, p<0.05).ConclusionIn this model exercise is beneficial to combat dyslipidemia and protect from atherosclerosis only when combined with diet.

Effect of Statin on the Reference Segments after Bare-Metal Stent Implantation

Effect of Statin on the Reference Segments after Bare-Metal Stent Implantation

Abstracted Proceedings from The International Cardiac Bioassist Conference, November 8-10, 2005, Fort Collins, Colorado, USA

Abstracted Proceedings from The International Cardiac Bioassist Conference, November 8-10, 2005, Fort Collins, Colorado, USA

Modulation du HDL-C et régression des plaques

High-density lipoproteins are distinct in exerting a wide range of anti-atherogenic actions at the arterial wall and in peripheral tissues. These actions include the capacity of HDL to facilitate efflux of cellular cholesterol in the process of reverse cholesterol transport and to mediate anti-inflammatory, antioxidative and anti-thrombotic effects. By contrast, atherogenic, cholesterol-rich lipoproteins containing apoB 100 (VLDL, VLDL remnants, IDL and LDL) penetrate the arterial intima and undergo retention, thus favoring cholesterol accumulation and atherosclerotic plaque formation. Despite the success of statin therapy in lowering atherogenic lipoprotein levels and thereby reducing cardiovascular morbi-mortality by up to 35% across a broad range of dyslipidaemic phenotypes in both primary and secondary prevention trials, demonstration of significant regression of atherosclerotic plaques in coronary arteries has been infrequent. Indeed, even in recent intervention trials involving intensive lipid lowering therapy in patients with coronary atherosclerosis, reduced atheroma progression -rather than significant plaque regression — was predominantly observed. What key mechanistic features might account for these findings? Potent statins act primarily to reduce circulating concentrations of atherogenic, apoB-containing lipoproteins (VLDL, VLDL remnants, IDL and LDL) by up to 50% or more. By contrast, statins fail to induce elevation in HDL to a similar degree, and indeed statin-induced raising of HDL cholesterol levels is typically in the range of 5-10%. Clearly then, statins are efficacious in reducing cholesterol influx into the arterial wall in the form of atherogenic lipoproteins, but do not appear to induce elevation of HDL to levels facilitating maximal efflux of cholesterol from cholesterol-rich atherosclerotic plaques. Indeed maximal rates of arterial cholesterol efflux to HDL concomitant with marked reduction in cholesterol influx and accumulation would be predicted to lead to significant plaque regression. In this context, it is especially relevant that recent in vivo findings in patients with acute coronary syndromes clearly suggest that infusion of HDL mimetic particles containing apoAI and phospholipids can lead to significant and rapid reduction of coronary atheroma plaque volume consistent with lesion regression. Such reduction in disease burden is suggestive of significant improvement in long term clinical outcome. Considered together, these findings clearly indicate that marked elevation of HDL-C may be a critical component of atherosclerosis regression. HDL therefore represents a key therapeutic target in atherogenic dyslipidaemia, a proposal consistent with epidemiological data (Framingham, PROCAM, ARIC) which have revealed that there is a potent and progressive reduction of coronary artery disease risk with increasing HDL-C levels.

The selective peroxisomal proliferator-activated receptor-gamma agonist has an additive effect on plaque regression in combination with simvastatin in experimental atherosclerosis: in vivo study by high-resolution magnetic resonance imaging

ObjectivesWe sought to investigate the anti-atherogenic effects of a selective peroxisomal proliferator-activated receptor-gamma (PPAR-gamma) agonist and simvastatin, as well as their combination, over time, in a rabbit model of experimental atherosclerosis. BackgroundThe PPARs are nuclear transcription factors that control a variety of cellular functions, with the potential effects required to induce plaque regression and stabilization. MethodsAtherosclerosis was induced in rabbits (n = 37) by the combination of double-balloon injury and a nine-month high-cholesterol (HC) diet. The rabbits were randomized into a continued HC diet, a normal chow (NC) diet, NC plus simvastatin, NC plus PPAR-gamma agonist, and NC plus simvastatin plus PPAR-gamma agonist. All rabbits underwent magnetic resonance imaging (MRI) at randomization and after six months of treatment and were then sacrificed for histopathologic study. ResultsAll groups had a similar vessel wall area by MRI (8.45 ± 0.65 mm2, p = NS between groups) at randomization. Significant progression was seen in the HC diet group (15 ± 4%, p < 0.01). In the NC and NC plus PPAR-gamma agonist groups, progression was abolished (−2.5 ± 3% and −4.5 ± 5%, respectively; p = NS). The NC plus simvastatin and NC plus simvastatin plus PPAR-gamma agonist groups had significant plaque regression (−12 ± 4% [p < 0.05] and −22 ± 4% [p < 0.01], respectively). Regression was independent of plasma lipid levels. All NC groups had similar lipid profiles at the end of treatment. Histopathologic analysis of the NC groups showed a decreased macrophage content and matrix metalloproteinase activity and an increased smooth muscle cell/collagen content of lesions. ConclusionsOur data indicate that normalization of plasma lipid levels abolishes progression of atherosclerosis. Simvastatin elicits regression of atherosclerotic lesions, and the combination simvastatin plus PPAR-gamma agonist has additive regression effects on plaque. This is paralleled by structural alterations in plaque composition, which may increase plaque stability. These observations support the beneficial effects of statins on atherosclerosis and show additional anti-atherogenic benefits of combining a PPAR-gamma agonist with simvastatin.

Carotid plaque regression on oestrogen replacement: A pilot study

To investigate the effect of unopposed oestrogen on atheromatous carotid plaques. Seventeen postmenopausal women with known carotid disease. Carotid intimal thickness and plaque length and thickness were measured prior to and following 3 and 6 months of treatment, using Duplex ultrasound. A total of 22 plaques were followed up. There was a reduction in plaque length after 3 (-8.14%, p = 0.001) and 6 months (-28%, p = 0.001) of treatment. The reduction in plaque thickness (-18%, p = 0.004) was significant after 6 months of treatment. Reductions in intimal thickness were not statistically significant. Our results suggest that oestrogen replacement is associated with significant plaque regression.