Plaque regression--a new target for antiatherosclerotic therapy.
Department of Cardiovascular Medicine, Cleveland Clinic Foundation, Cleveland, OhioAmerican heart journal (Impact Factor: 4.56). 04/2005; 149(3):384-7. DOI: 10.1016/j.ahj.2004.11.003
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ABSTRACT: Some modern angioplasty techniques drastically affect the geometry of the plaque and the lumen, but have some inherent clinical and technical limitations. A total of 101 Yucatan miniature swine were allocated to the three following groups (34 pigs into 60/15- to 70/40-nm silica-gold nanoparticles (NPs), 34 swine into ferromagnetic group with iron-bearing NPs and delivery in hand of magnetic fields, and 33 in a sirolimus stenting control). Animals in the nanogroup were subdivided further into four subsets according to the delivery approach: (1) Intracoronary infused circulating stem progenitor cells (SPCs), including SP(+) (side population) cells, (2) intracoronary infused, ultrasound-mediated, albumin-coated, gas-filled microbubbles, (3) CD73(+)105(+) SPCs in the composition of a bioengineered on-artery patch (cardiac surgery), (4) CD73(+)CD105(+) SPCs engrafted by manual subadventitial injection (cardiac surgery). NPs were detonated with a microwatt near-infrared (NIR) laser (821 nm, 35-44 W/cm(2) for 7 min of exposure). Changes of the total atheroma volume (TAV; mm(3)) immediately after the laser irradiation at month 6 in the nanoshell, ferromagnetic, and control groups were -7.54%/-22.92%, -9.7%/-16.84%, and -10.5%/-7.06% (p<0.01), respectively, and in the subsets reached -2.79%/-21.92%, -6.26%/-15.24%, -4.6%/-31.21%, -16.5%/-23.3% (p<0.05), respectively. Some cases of atherothrombosis and distal embolism (23.5%) were documented only in the microbubbles subset. The impact of the therapy on the nonorganic part of the plaque-antiinflammative and antiapoptotic effects, signs of neovascularization, and restoration of artery function-were predominant in the observed subsets with SPCs (p<0.01). Nanoburning, especially in combination with stem cell technologies, is a very challenging technique for altering advanced plaque and holds the promise of revolutionizing state-of-the-art interventional cardiology, assuring destruction of plaque and functional restoration of the vessel wall. It could potentially become the current mechanical and pharmacological treatment.Rejuvenation Research 04/2012; 15(2):222-30. · 2.92 Impact Factor
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ABSTRACT: Patients with metabolic syndrome are at increased risk for cardiovascular complications. We sought to determine whether peroxisome proliferator-activated receptor gamma agonists had any beneficial effect on patients with metabolic syndrome undergoing percutaneous coronary intervention (PCI). A total of 200 patients with metabolic syndrome undergoing PCI were randomized to rosiglitazone or placebo and followed for 1 year. Carotid intima-medial thickness (CIMT), inflammatory markers, lipid levels, brain natriuretic peptide, and clinical events were measured at baseline, 6 months, and 12 months. There was no significant difference in CIMT between the 2 groups. There was no difference in the 12-month composite end point of death, myocardial infarction (MI), stroke, or any recurrent ischemia (31.4% vs 30.2%, P = .99). The rate of death, MI, or stroke at 12 months was numerically lower in the rosiglitazone group (11.9% vs 6.4%, P = .19). There was a trend toward a greater decrease over time in high-sensitivity C-reactive protein values compared with baseline in the group randomized to rosiglitazone versus placebo both at 6 months (-35.4% vs -15.8%, P = .059) and 12 months (-40.0% vs -20.9%, P = .089) and higher change in high-density lipoprotein (+15.5% vs +4.1%, P = .05) and lower triglycerides (-13.9% vs +14.9%, P = .004) in the rosiglitazone arm. There was a trend toward less new onset diabetes in the rosiglitazone group (0% vs 3.3%, P = .081) and no episodes of symptomatic hypoglycemia. There was no excess of new onset of clinical heart failure in the rosiglitazone group, nor was there a significant change in brain natriuretic peptide levels. Patients with metabolic syndrome presenting for PCI are at increased risk for subsequent cardiovascular events. Rosiglitazone for 12 months did not appear to affect CIMT in this population, although it did have beneficial effects on high-sensitivity C-reactive protein, high-density lipoprotein, and triglycerides. Further study of peroxisome proliferator-activated receptor agonism in patients with metabolic syndrome undergoing PCI may be warranted.American heart journal 08/2007; 154(1):137-43. · 4.56 Impact Factor
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ABSTRACT: Statins do not always decrease coronary heart disease mortality, which was speculated based on increased serum plant sterols observed during statin treatment. To evaluate plant sterol atherogenicity, we fed low density lipoprotein-receptor deficient (LDLr(+/-)) mice for 35 weeks with Western diets (control) alone or enriched with atorvastatin or atorvastatin plus plant sterols or stanols. Atorvastatin decreased serum cholesterol by 22% and lesion area by 57%. Adding plant sterols or stanols to atorvastatin decreased serum cholesterol by 39% and 41%. Cholesterol-standardized serum plant sterol concentrations increased by 4- to 11-fold during sterol plus atorvastatin treatment versus stanol plus atorvastatin treatment. However, lesion size decreased similarly in the sterol plus atorvastatin (-99% vs. control) and the stanol plus atorvastatin (-98%) groups, with comparable serum cholesterol levels, suggesting that increased plant sterol concentrations are not atherogenic. Our second study confirms this conclusion. Compared with lesions after a 33 week atherogenic period, lesion size further increased in controls (+97%) during 12 more weeks on the diet, whereas 12 weeks with the addition of plant sterols or stanols decreased lesion size (66% and 64%). These findings indicate that in LDLr(+/-) mice 1) increased cholesterol-standardized serum plant sterol concentrations are not atherogenic, 2) adding plant sterols/stanols to atorvastatin further inhibits lesion formation, and 3) plant sterols/stanols inhibit the progression or even induce the regression of existing lesions.The Journal of Lipid Research 01/2007; 47(12):2762-71. · 4.73 Impact Factor
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