Endothelial Plaque Research Articles

Clinical features and treatments of retrocorneal fungal infection

Objective: To evaluate the clinical features of retrocorneal fungal infection and the therapeutic effects. Methods: This was a retrospective, noncomparative study of nine patients with retrocorneal fungal infection and an intact corneal epithelium treated at Qingdao Eye Hospital. The history, clinical features, diagnostic methods, pathogens and therapeutic effects were analyzed. Results: Five patients had a history of trauma by plant, two had a non-plant injury, and two had unidentified reasons. The duration between the initial onset and the first visit to our hospital was 7.9 months (range, 3 months to 2 years). There was endothelial plaque and sometimes with white infiltration in the deep stroma, but the corneal epithelium remained integrated, and the anterior stroma was uninfected. The patients were misdiagnosed as uveitis, herpes simplex keratitis or bacterial keratitis in the other hospitals. Visual acuity was 20/200 in four eyes, 20/60 in one eye, 20/40 in two eyes, and 20/30 in two eyes. Fungal hyphae were detected by confocal microscopy in six eyes. All the eyes had poor response to the antifungal medication before penetrating keratoplasty was performed. The smear examinations of the corneal endothelial plaque showed fungal hyphae in six eyes. Alternaria Nees, Apospory, Phialophora verrucosa, and Fusarium were identified. Conclusions: Plant injury is the most common risk factor of retrocorneal fungal infection. Slow onset and no initially obvious symptoms may lead to delayed diagnosis and misdiagnosis. The diagnosis can be confirmed by confocal microscopy before surgery. The effect of antifungal medication is usually poor. (Chin J Ophthalmol, 2017, 53:758-765).

Role of Low Endothelial Shear Stress and Plaque Characteristics in the Prediction of Nonculprit Major Adverse Cardiac Events: The PROSPECT Study

ObjectivesThis study sought to determine whether low endothelial shear stress (ESS) adds independent prognostication for future major adverse cardiac events (MACE) in coronary lesions in patients with high-risk acute coronary syndrome (ACS) from the United States and Europe. BackgroundLow ESS is a proinflammatory, proatherogenic stimulus associated with coronary plaque development, progression, and destabilization in human-like animal models and in humans. Previous natural history studies including baseline ESS characterization investigated low-risk patients. MethodsIn the PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study, 697 patients with ACS underwent 3-vessel intracoronary imaging. Independent predictors of MACE attributable to untreated nonculprit (nc) coronary lesions during 3.4-year follow-up were large plaque burden (PB), small minimum lumen area (MLA), and thin-cap fibroatheroma (TCFA) morphology. In this analysis, baseline ESS of nc lesions leading to new MACE (nc-MACE lesions) and randomly selected control nc lesions without MACE (nc-non-MACE lesions) were calculated. A propensity score for ESS was constructed for each lesion, and the relationship between ESS and subsequent nc-MACE was examined. ResultsA total of 145 lesions were analyzed in 97 patients: 23 nc-MACE lesions (13 TCFAs, 10 thick-cap fibroatheromas [ThCFAs]), and 122 nc-non-MACE lesions (63 TCFAs, 59 ThCFAs). Low local ESS (<1.3 Pa) was strongly associated with subsequent nc-MACE compared with physiological/high ESS (≥1.3 Pa) (23 of 101 [22.8%]) versus (0 of 44 [0%]). In propensity-adjusted Cox regression, low ESS was strongly associated with MACE (hazard ratio: 4.34; 95% confidence interval: 1.89 to 10.00; p < 0.001). Categorizing plaques by anatomic risk (high risk: ≥2 high-risk characteristics PB ≥70%, MLA ≤4 mm2, or TCFA), high anatomic risk, and low ESS were prognostically synergistic: 3-year nc-MACE rates were 52.1% versus 14.4% versus 0.0% in high-anatomic risk/low-ESS, low-anatomic risk/low-ESS, and physiological/high-ESS lesions, respectively (p < 0.0001). No lesion without low ESS led to nc-MACE during follow-up, regardless of PB, MLA, or lesion phenotype at baseline. ConclusionsLocal low ESS provides incremental risk stratification of untreated coronary lesions in high-risk patients, beyond measures of PB, MLA, and morphology.

Risk factors, demographics and clinical profile of Acanthamoeba keratitis in Melbourne: an 18-year retrospective study

PurposeTo assess incidence, risk factors, presentation and final visual outcome of patients with Acanthamoebakeratitis (AK) treated at the Royal Victorian Eye and Ear Hospital (RVEEH), Melbourne, Australia, over an 18-year...

P3468Coronary microvascular endothelial dysfunction is associated with low endothelial shear stress and high-risk coronary plaque characteristics in patients with early coronary atherosclerosis

P3468Coronary microvascular endothelial dysfunction is associated with low endothelial shear stress and high-risk coronary plaque characteristics in patients with early coronary atherosclerosis

Curvularia Keratomycosis after Cataract Surgery

Introduction: Curvularia is an emerging dematiaceous/melanized/phaeoid hyphomycete causing ocular curvulariosis including keratomycosis, conjunctivitis, dacryocystitis, sino-orbital cellulitis, and endophthalmitis. Curvularia ketatomycosis may be associated with satellite stromal infiltrates, immune rings, Descement’s folds, iriditis, and endothelial plaque. Surgical trauma followed by delayed tissue healing may render cornea susceptible to invasion by exogenous air-dispersed conidia from environment. Cases Presentation: Curvularia lunata keratomycosis occurred in 2 military veterans after phacoemulsification and intraocular lens implantation without any history of trauma. Topical 5% natamycin was effective for treatment resulting in minimal residual scar. Complete recovery and uneventful 1-year follow-up period was observed. Conclusions: Seven out of 30 Curvularia species are emerging as opportunistic human pathogens from being primary phytopathogens. With increasing ocular surgeries in the diabetic populace amongst general population including military veterans, a high index of clinical and microbiological suspicion is required for optimal diagnosis of emerging pathogens in post-operative keratomycosis. Keywords: Keratomycosis; Cataract Surgery; Curvularia lunata

Effects of combination therapy of tirofiban and reteplase on endothelial function, coagulation function and inflammatory factors in elderly patients with acute ST-segment elevation myocardial infarction

Objective To investigate the effect of the combination therapy of tirofiban and reteplase on endothelial function, coagulation function and plaque inflammation in elderly patients with ST-elevation acute myocardial infarction (STEMI). Methods 100 patients with STEMI were treated with percutaneous transluminal coronary intervention (PCI) from January 2014 to June 2016 in our hospital.39 cases in the control group used conventional oral aspirin, clopidogrel and statins and other treatment.61 cases in the observation group received tirofiban and reteplase on the basis of the control group.The expression of endothelial microparticles (EMP) was detected by flow cytometry (FCM), and the ICAM-1, high sensitivity C-reactive protein (hs-CRP), tumor necrosis factor α(TNF-α) and interleukin-6 (IL-6), endothelin-1(ET-1) were measured by enzyme-linked immunosorbent assay (ELISA). The thrombin time (TT), activated partial thrombin time (APTT), prothrombin time (PT) and other indicators were measured by PUN-2048A coagulation instrument, then statistical analysis was performed. Results The postoperative levels of EMP, ICAM-1 and ET-1 of control group were (693.46±90.72), (768.58±20.46)μg/L and (31.27±8.18)ng/L, which were significantly higher than those in the observation group [(652.36±67.39), (752.37±25.0)μg/L, (28.22±5.05)ng/L], the differences were statistically significant (t=2.41, 2.67, 2.68, all P<0.05). After operation, the hs-CRP, TNF-α, IL-6 levels in the control group were (4.16±2.35)mg/L, (4.32±2.02)ng/L, (10.59±3.16)ng/mL, which were significantly higher than those in the observation group [(2.22±1.47)mg/L, (2.74±1.52)ng/L, (6.33±2.24)ng/mL], the differences were statistically significant(t=2.65, 2.67, 3.42, all P<0.05). The postoperative TT, PT, APTT in the observation group were (26.31±3.18)s, (14.34±1.67)s, (27.20±4.12)s, which were significantly longer than those in the control group [(24.03±2.84)s, (12.56±1.43)s, (24.55±3.62)s], the differences were statistically significant(t=2.15, 2.31, 2.65, all P<0.05). Conclusion Tirofiban combined with reteplase can improve endothelial function, inhibit inflammatory reaction and regulate coagulation function. Key words: Myocardial infarction; Platelet membrane glycoprotein IIb; Tirofiban hydrochloride; Reteplase

Low dose dietary nitrate improves endothelial dysfunction & plaque stability in the ApoE-/- mouse fed a high fat diet

Low dose dietary nitrate improves endothelial dysfunction & plaque stability in the ApoE-/- mouse fed a high fat diet

Endothelial progenitor cells and plaque burden in stented coronary artery segments: an optical coherence tomography study six months after elective PCI

BackgroundEndothelial progenitor cells (EPC) are involved in neovascularization and endothelial integrity. They might be protective in atherosclerosis. Optical coherence tomography (OCT) is a precise intracoronary imaging modality that allows assessment of subintimal plaque development. We evaluated the influence of EPC on coronary plaque burden in stable disease and implemented a novel computational plaque analysis algorithm using OCT.MethodsForty-three patients (69.8% males, 69.6 ± 7.7 years) were investigated by OCT during re-angiography 6 months after elective stent implantation. Different subpopulations of EPCs were identified by flow cytometry according to their co-expression of antigens (CD34+, CD133+, kinase domain receptor, KDR+). An algorithm was applied to calculate the underlying total plaque burden of the stented segments from OCT images. Plaque morphology was assessed according to international consensus in OCT imaging.ResultsA cumulative sub-strut plaque volume of 10.87 ± 12.7 mm3 and a sub-stent plaque area of 16.23 ± 17.0 mm2 were found within the stented vessel segments with no significant differences between different stent types. All EPC subpopulations (mean of EPC levels: CD34+/CD133+: 2.66 ± 2.0%; CD34+/KDR+: 7.50 ± 5.0%; CD34+/CD133+/KDR+: 1.12 ± 1.0%) inversely correlated with the identified underlying total plaque volume and plaque area (p ≤ 0.012).ConclusionsThis novel analysis algorithm allows for the first time comprehensive quantification of coronary plaque burden by OCT and illustration as spread out vessel charts. Increased EPC levels are associated with less sub-stent coronary plaque burden which adds to previous findings of their protective role in atherosclerosis.

Faktori rizika za nastanak ateroskleroze u svetlu postojećih naučnih saznanja

Atherosclerosis is a progressive, multifactorial, diffuse, multisystemic, chronic, inflammatory disease, which is manifested by disorders of vascular, immune and metabolic system. Atherosclerosis is a disease of the large and intermediate sized arteries in which one can observe five stages (endothelial dysfunction, fatty stain, transitory lesion, fibrotic plaque and complex lesion). Pathogenesis of this disease is not fully understood. Numerous scientific theories, as well as functional, experimental and clinical studies try to explain pathogenesis of atherosclerosis, whose the frequentative consequences, coronary disease and cerebral infarction, are currently the leading worldwide cause of death. In this review, we provide an overview of recent literature data and practical knowledge related to most important risk factors for atherosclerosis. Having in mind increase of prevalence of atherosclerosis and its complications in future, it is necessary to take preventive actions to decrease risk factors (inappropriate diet rich in carbohydrates and saturated fat, obesity, smoking, sedentary lifestyle and physical inactivity). Except to lifestyle changes, usage of hypocaloric diet and increase level of physical activity, in patients with progressive atherosclerosis it is necessary to apply appropriate medical treatment.

Low dose dietary nitrate improves endothelial dysfunction and plaque stability in the ApoE−/− mouse fed a high fat diet

BackgroundNitric oxide (NO) is an important vascular signalling molecule. NO is synthesised endogenously by endothelial nitric oxide synthase (eNOS). An alternate pathway is exogenous dietary nitrate, which can be converted to nitrite and then stored or further converted to NO and used immediately. Atherosclerosis is associated with endothelial dysfunction and subsequent lesion formation. This is thought to arise due to a reduction in the bioavailability and/or bioactivity of endogenous NO. AimTo determine if dietary nitrate can protect against endothelial dysfunction and lesion formation in the ApoE−/− mouse fed a high fat diet (HFD). Methods and resultsApoE−/− fed a HFD were randomized to receive (i) high nitrate (10mmol/kg/day, n=12), (ii) moderate nitrate (1mmol/kg/day, n=8), (iii) low nitrate (0.1mmol/kg/day, n=8), or (iv) sodium chloride supplemented drinking water (control, n=10) for 10 weeks. A group of C57BL6 mice (n=6) received regular water and served as a healthy reference group. At 10 weeks, ACh-induced vessel relaxation was significantly impaired in ApoE−/− mice versus C57BL6. Mice supplemented with low or moderate nitrate showed significant improvements in ACh-induced vessel relaxation compared to ApoE−/− mice given the high nitrate or sodium chloride. Plaque collagen expression was increased and lipid deposition reduced following supplementation with low or moderate nitrate compared to sodium chloride, reflecting increased plaque stability with nitrate supplementation. Plasma nitrate and nitrite levels were significantly increased in all three groups fed the nitrate-supplemented water. ConclusionLow and moderate dose nitrate significantly improved endothelial function and atherosclerotic plaque composition in ApoE−/− mice fed a HFD.

Effect of chronic inflammation on coronary arteries in renal amyloidosis: More than renal dysfunction

Effect of chronic inflammation on coronary arteries in renal amyloidosis: More than renal dysfunction

Aqueous Terminalia arjuna extract modulates expression of key atherosclerosis-related proteins in a hypercholesterolemic rabbit: A proteomic-based study.

The present study evaluates the effect of an aqueous extract of Terminalia arjuna (aqTAE) on protein expression in aortic plaques of hypercholesterolemic rabbits using a proteomic approach. Thirty male New Zealand rabbits (n = 6) were employed as Gp1 (stock diet); Gp2 (high-fat diet [HFD]); Gp3 (stock diet + aqTAE); Gp4 (HFD + aqTAE); and Gp5 (HFD + atorvastatin) and followed for 6 months. Protein lysates of aortic tissues were separated by 2DE and proteins were identified by MALDI-TOF/MS. Serum lipids were found to be significantly increased by an HFD and reduced by aqTAE both at 3 and 6 months (Gp4 vs. Gp2; p < 0.05). Total 79 spots were differentially expressed, among which 60 individual proteins were identified, 31 grouped as atherosclerosis-related proteins and 29 classified as others. aqTAE significantly attenuated the protein expression of tumor necrosis factor α, cyclooxygenase-2, MMP-9, HSP60, ICAM-5, Endothelin-3, Vimentin, Protein S100-A9 besides others. Many of the observed proteins are known to be consistently associated with endothelial dysfunction, inflammation, plaque rupture, and immune imbalance. Strong hypolipidemic effects of aqTAE and attenuation of these signature atherogenic biomarkers using proteomics highlights the fact that aqTAE may be useful in the prevention and management of atherosclerosis.

Abstract 8: The Membrane-associated Guanylate Kinase Ww and Pdz Domain-containing Protein 1 magi1 is Required for Disturbed Flow-induced Endothelial Inflammation and Atherosclerotic Plaque Formation

Rationale: Major chronic inflammatory diseases including inflammatory bowel disease and psoriasis are clinically associated with accelerated atherosclerosis and increased risk of cardiovascular diseases (CVD). Atherosclerosis has long been recognized as an inflammatory process, which is initiated by the inflammation and dysfunction of endothelial cells (ECs). Genome-wide association study (GWAS) has identified a significant association between the deletion in ADAMTS9-MAGI1 locus with inflammatory bowel disease and psoriasis, suggesting a potential involvement of MAGI1 in EC inflammation and its associated events. Objective: To investigate the role and regulatory mechanism of MAGI1 as well as MAGI1 post-translational modification in EC inflammation, after various pro-atherogenic stimuli. Methods and Results: MAGI1 depletion significantly inhibits NF-κB activation and adhesion molecule expression induced by various pro-atherogenic stimuli in both in vitro and in vivo . We show that p90RSK associates with MAGI1 WW and PDZ2 domain, which is a crucial step for EC inflammation. In addition, p90RSK activation independently regulates MAGI1 S741 phosphorylation and K931 de-SUMOylation. While MAGI1 S741 phosphorylation is vital for Rap1 and subsequent NF-kB activation via increasing MAGI1-RAPGEF2 interaction, MAGI1 de-SUMOylation induces p90RSK-MAGI1 nuclear translocation as well as nuclear SENP2 T368 and ERK5 S496 phosphorylation. Those events are critical for EC inflammation. In addition, in partial carotid ligation mouse model, we observed a reduction in size of disturbed flow-induced carotid plaque lesion in Magi1 +/- / Ldlr -/- mice compared to that in Magi1 +/+ / Ldlr -/- mice fed with high fat diet, indicating the crucial role of MAGI1 in regulating EC inflammation and atherosclerosis formation. Conclusion: These data show the essential role of MAGI1 in regulating EC inflammation, and suggest that phosphorylation and de-SUMOylation of MAGI1 induced by p90RSK activation have distinctive mechanisms, leading to EC inflammation.

Tooth brushing for a longer and healthier life.

Tooth brushing for a longer and healthier life.

Atheroprotective effects of pure tocotrienol supplementation in the treatment of rabbits with experimentally induced early and established atherosclerosis

BackgroundAtherosclerosis is the main cause of coronary artery disease -related deaths worldwide. The atheroprotective properties of pure tocotrienols (T3) in the absence of alpha-tocopherol (α-TCP) in vitamin E has not been extensively examined.AimTo determine the atheroprotective properties of T3 in early and established atherosclerosis rabbits.MethodsThirty New Zealand white rabbits were divided into two groups, B1 and B2 which represent early [fed 1% high cholesterol diet (HCD) for 2 weeks] and established (fed 1% HCD for 8 weeks) atherosclerosis. Each group was subdivided into three intervention arms: 1) T3–4 mg/kg, 2) T3–15 mg/kg and 3) vehicle without T3 (T3 negative) for 8 weeks. Serial fasting blood samples were obtained for lipid profile, and whole lengths of aorta were used to determine tissue markers of endothelial activation, inflammation and plaque stability.ResultsIn B1, atherosclerotic lesion in T3–4 mg/kg group was significantly reduced (p=0.008), while aortic tissue expression of vascular cellular adhesion molecule 1 (VCAM-1), interleukin-6 (IL-6) and matrix metalloproteinase (MMP-12) was reduced in T3–4 mg/kg compared to T3-negative rabbits group (0.2±0.1 vs. 28.5±3.1%; 3.0±1.6 vs. 14.0±1.7%; and 5.2±2.2 vs. 27.7±0.8%, respectively, p<0.05). T3–15 mg/kg group showed reduction in VCAM-1, E-selectin, IL-6 and MMP-12 (3.9±1.9 vs. 28.5±3.1%; 10.3±0.5 vs. 59.8±8.5%; 2.6±1.7 vs. 14.0±1.7%; and 16.2±3.2 vs. 27.7 0.8%, respectively, p<0.05). In B2, T3–4 mg/kg group reduced aortic tissue expression of intercellular adhesion molecule 1 (ICAM-1), E-selectin, IL-6, MMP-12 and MMP-9 compared to T3-negative rabbits group (29.9±2.4 vs. 55.3±1.3%; 26.7±1.5 vs. 60.5±7.6%; 15.7±0.7 vs. 27.7±4.8%; 34.8±2.7 vs. 46.5±3.4%; and 25.89±3.9 vs. 45.9±1.7%, respectively, p<0.05). T3–15 mg/kg group showed reduced VCAM-1, ICAM-1, E-selectin, IL-6, MMP-12 and MMP-9 (20.5±3.3 vs. 35.6±2.5%; 24.9±1.3 vs. 55.3±1.3%; 29.9±6.7 vs. 60.5±7.6; 11.3±2.2 vs. 27.7±4.8%; 23.0±1.7 vs. 46.5±3.4%; and 17.6±1.9 vs. 45.9±1.7%, respectively, p<0.05.ConclusionThese findings suggest the possible atheroprotective role T3 plays as an adjunct supplementation to standard treatment in the prevention of CAD.

Development of Antiatherosclerotic Drugs on the Basis of Cell Models: A Comment

The large research series has become internationally known in the 1980s and continues until today. Cultures of cultured or incubated smooth muscle cells or monocytes/macrophages were used for the measurement of capacities of substances to enhance or lower intracellular cholesterol deposition, which was interpreted as anti-or pro-atherogenic action. The LDL from patients with coronary atherosclerosis caused a 2-4 times elevation of cholesterol contents within the cultured cells. Incubation with sera or LDL from healthy subjects did not induce cholesterol accumulation. Various drugs and natural substances were found to possess pro-or anti-atherogenic potencies. Anti-atherogenic effect of different preparations of plant origin was reported: if an agent induced intracellular lipid accumulation it was regarded atherogenic and vice versa. However, if a pharmacological agent lowers the uptake of lipids by cells in a culture, it should be expected to increase the blood cholesterol level in vivo. It can be reasonably assumed that a drug, inhibiting cholesterol uptake by cultured cells, would elevate the blood cholesterol level in vivo. By analogy with familial hypercholesterolemia, it might contribute to atherosclerosis: lipids would be deposited into the intercellular/subendothelial space of the vascular wall, in sites with damaged endothelial barrier and vulnerable plaques. The agents supposedly having an anti-atherogenic potency in a cell culture might reduce cholesterol uptake diffusely by entire cell populations contributing thereby to hypercholesterolemia. On the contrary, atherosclerosis is a focal disease, affecting primarily damaged sites of the vascular lining, which would be favored by hypercholesterolemia.

Impact of top end anastomosis design on patency and flow stability in coronary artery bypass grafting.

For coronary artery bypass grafting (CABG), free grafts such as a saphenous vein or radial artery are often used for grafts to the lateral and posterior walls. However, the relationship between top-end anastomosis design and long-term patency remains unknown. Because coronary artery blood flow is dominant during diastole, top-end anastomosis may work better if the graft is directed towards the apex, whereas the shortest graft pathway appears to be most efficient. Using computational fluid dynamic models, we evaluated the hemodynamic variables that were affected by the angle of the top-end anastomosis. We created three-dimensional geometries of the aortic root with coronary arteries that involved 75% stenosis in the obtuse marginal and postero-lateral branches. Two bypass models under vasodilator administration were created: in a"Model A", the top-end anastomosis is parallel to the long axis of the ascending aorta and the graft passed over the conus directed towards the apex; in a "Model B", the top-end anastomosis is directed toward the shortest pathway, and form near the right angles to the long axis of the ascending aorta. Wall shear stress (WSS) and its fluctuation, an oscillatory shear index (OSI) were evaluated to predict fibrosis progression at the anastomosis site and graft flow. Graft flow was 197.3ml/min and 207.3ml/min in the "Model A" and "Model B", respectively. The minimal WSS value inside the graft with the "Model A" and "Model B" was 0.53Pa and 4.09Pa, respectively, and the OSI value was 0.46 and 0.04, respectively. The top-end anastomosis of a free graft should be directed vertically towards the aorta to achieve the shortest graft pathway to maintain a high graft flow rate and to avoid the risks of endothelial fibrosis and plaque progression over the long-term after CABG.

SEX DIFFERENCES IN CORONARY PATHOPHYSIOLOGY IN PATIENTS WITH ANGINA IN THE ABSENCE OF OBSTRUCTIVE CORONARY ARTERY DISEASE

Sex differences in coronary pathophysiology have been suggested, but these data are mostly from all women studies. We investigated sex differences in endothelial dysfunction, microvascular dysfunction (MVD), plaque burden, and myocardial bridging (MB) in women and men presenting with angina in the

Inflammation, oxidative stress and renin angiotensin system in atherosclerosis.

Atherosclerosis is a chronic inflammatory disease associated with cardiovascular dysfunction including myocardial infarction, unstable angina, sudden cardiac death, stroke and peripheral thromboses. It has been predicted that atherosclerosis will be the primary cause of death in the world by 2020. Atherogenesis is initiated by endothelial injury due to oxidative stress associated with cardiovascular risk factors including diabetes mellitus, hypertension, cigarette smoking, dyslipidemia, obesity, and metabolic syndrome. The impairment of the endothelium associated with cardiovascular risk factors creates an imbalance between vasodilating and vasoconstricting factors, in particular, an increase in angiotensin II (Ang II) and a decrease in nitric oxide. The renin-angiotensin system (RAS), and its primary mediator Ang II, also have a direct influence on the progression of the atherosclerotic process via effects on endothelial function, inflammation, fibrinolytic balance, and plaque stability. Anti-inflammatory agents [statins, secretory phospholipase A2 inhibitor, lipoprotein-associated phospholipase A2 inhibitor, 5-lipoxygenase activating protein, chemokine motif ligand-2, C-C chemokine motif receptor 2 pathway inhibitors, methotrexate, IL-1 pathway inhibitor and RAS inhibitors (angiotensin-converting enzyme inhibitors)], Ang II receptor blockers and ranin inhibitors may slow inflammatory processes and disease progression. Several studies in human using anti-inflammatory agents and RAS inhibitors revealed vascular benefits and reduced progression of coronary atherosclerosis in patients with stable angina pectoris; decreased vascular inflammatory markers, improved common carotid intima-media thickness and plaque volume in patients with diagnosed atherosclerosis. Recent preclinical studies have demonstrated therapeutic efficacy of vitamin D analogs paricalcitol in ApoE-deficient atherosclerotic mice.

Mesenchymal Stem Cells Ameliorate Atherosclerotic Lesions via Restoring Endothelial Function.

Transplantation of mesenchymal stem cells (MSCs) is beneficial in myocardial infarction and hind limb ischemia, but its ability to ameliorate atherosclerosis remains unknown. Here, the effects of MSCs on inhibiting endothelial dysfunction and atherosclerosis were investigated in human/mouse endothelial cells treated with oxidized low-density lipoprotein (oxLDL) and in apolipoprotein E-deficient (apoE-/-) mice fed a high-fat diet. Treatment with oxLDL inactivated the Akt/endothelial nitric-oxide synthase (eNOS) pathway, induced eNOS degradation, and inhibited nitric oxide (NO) production in endothelial cells. Coculture with human MSCs reversed the effects of oxLDL on endothelial cells and restored Akt/eNOS activity, eNOS level, and NO production. Reduction of endothelium-dependent relaxation and subsequent plaque formation were developed in apoE-/- mice fed a high-fat diet. Systemic infusion with mouse MSCs ameliorated endothelial dysfunction and plaque formation in high-fat diet-fed apoE-/- mice. Interestingly, treatment with interleukin-8 (IL8)/macrophage inflammatory protein-2 (MIP-2) alone induced the similar effects of human/mouse MSCs on oxLDL-treated human/mouse endothelial cells. Neutralization antibodies (Abs) against IL8/MIP-2 also blocked the effects of human/mouse MSCs on oxLDL-treated human/mouse endothelial cells. Consistently, MIP-2 injection alone induced the similar effect of MSCs on the endothelial function in high-fat diet-fed apoE-/- mice. The improvement in endothelial dysfunction by mouse MSCs was also blocked when pretreating MSCs with anti-MIP-2 Abs. In conclusion, MSC transplantation improved endothelial function and plaque formation in high-fat diet-fed apoE-/- mice. Activation of the Akt/eNOS pathway in endothelium by IL8/MIP-2 is involved in the protective effect of MSCs. The study helps support the use and clarify the mechanism of MSCs for ameliorating atherosclerosis.