Search PubMed⌕ Search

Biomedical subjects

Pedro R Moreno

Publications and source records attributed to Pedro R Moreno.

At least 19 recordsLinked to original sources
PubMed2006

Haptoglobin genotype is a determinant of iron, lipid peroxidation, and macrophage accumulation in the atherosclerotic plaque.

OBJECTIVE: Intraplaque hemorrhage increases the risk of plaque rupture and thrombosis. The release of hemoglobin (Hb) from extravasated erythrocytes at the site of hemorrhage leads to iron deposition, which may increase oxidation and inflammation in the atherosclerotic plaque. The haptoglobin (Hp) protein is critical for protection against Hb-induced injury. Two common alleles exist at the Hp locus and the Hp 2 allele has been associated with increased risk of myocardial infarction. We have demonstrated decreased anti-oxidative and anti-inflammatory activity for the Hp 2 protein. We tested the hypothesis that the Hp 2-2 genotype is associated with increased oxidative and macrophage accumulation in atherosclerotic plaques. METHODS AND RESULTS: The murine Hp gene is a type 1 Hp allele. We created a murine type 2 Hp allele and targeted its insertion to the Hp locus by homologous recombination. Atherosclerotic plaques from C57Bl/6 ApoE-/- Hp 2-2 mice were associated with increased iron (P=0.008), lipid peroxidation (4-hydroxynonenal and ceroid) and macrophage accumulation (P=0.03) as compared with plaques from C57Bl/6 ApoE-/- Hp 1-1 mice. CONCLUSIONS: Increased iron, lipid peroxidation and macrophage accumulation in ApoE-/- Hp 2-2 plaques suggests that the Hp genotype plays a critical role in the oxidative and inflammatory response to intraplaque hemorrhage.

Alleles↗
PubMed2006

Atherosclerosis.

Explore the source record for details and available documents.

Atherosclerosis↗
PubMed2005

Atherothrombosis and high-risk plaque: Part II: approaches by noninvasive computed tomographic/magnetic resonance imaging.

This second part of the review on atherothrombosis highlights the diffuse nature of the disease analyzing the feasibility and potential of the noninvasive imaging modalities, including computed tomography (electron-beam computed and multi-detector computed tomography) and magnetic resonance imaging for its detection and monitoring. These imaging modalities are being established as promising tools in high-risk cardiovascular patients for identification and/or management of coronary calcification, stenotic or obstructive disease, high-risk plaques (not necessarily stenotic), and overall burden of the disease. In addition, such technology facilitates the understanding of the processes involved in the development and progression of atherothrombosis responsible for coronary, cerebral, and peripheral ischemic events.

Atherosclerosis↗
PubMed2005

Atherothrombosis and high-risk plaque: part I: evolving concepts.

Atherothrombosis is a complex disease in which cholesterol deposition, inflammation, and thrombus formation play a major role. Rupture of high-risk, vulnerable plaques is responsible for coronary thrombosis, the main cause of unstable angina, acute myocardial infarction, and sudden cardiac death. In addition to rupture, plaque erosion may also lead to occlusive thrombosis and acute coronary events. Atherothrombosis can be evaluated according to histologic criteria, most commonly categorized by the American Heart Association (AHA) classification. However, this classification does not include the thin cap fibroatheroma, the most common form of high-risk, vulnerable plaque. Furthermore, the AHA classification does not include plaque erosion. As a result, new classifications have emerged and are reviewed in this article. The disease is asymptomatic during a long period and dramatically changes its course when complicated by thrombosis. This is summarized in five phases, from early lesions to plaque rupture, followed by plaque healing and fibrocalcification. For the early phases, the role of endothelial dysfunction, cholesterol transport, high-density lipoprotein, and proteoglycans are discussed. Furthermore, the innate and adaptive immune response to autoantigens, the Toll-like receptors, and the mechanisms of calcification are carefully analyzed. For the advanced phases, the role of eccentric remodeling, vasa vasorum neovascularization, and mechanisms of plaque rupture are systematically evaluated. In the final thrombosis section, focal and circulating tissue factor associated with apoptotic macrophages and circulatory monocytes is examined, closing the link between inflammation, plaque rupture, and blood thrombogenicity.

Atherosclerosis↗
PubMed2005

Chronic thrombus detection with in vivo magnetic resonance imaging and a fibrin-targeted contrast agent.

BACKGROUND: Arterial thrombosis plays a critical role in acute coronary syndromes and stroke. Therefore, the ability to detect thrombus in vivo has a significant clinical implication. Magnetic resonance imaging (MRI) has shown promise in noninvasive thrombus detection. However, thrombus characterization and age definition remain difficult. We sought to evaluate the use of a fibrin-targeted peptide (EP-2104R) for MR thrombus detection and to compare this modality with non-contrast-enhanced (NCE) MRI and with Gd-DTPA injection at various ages and time points after thrombus generation. METHODS AND RESULTS: Carotid artery thrombosis was induced by external injury and stasis in 18 rabbits. T1-weighted MRI was performed before and after contrast agent injection, within 6 hours of thrombus induction, at 48 hours, at 1 week, and every week up to 8 weeks after injury. Correlation with histopathology was performed. The fibrin-targeted contrast agent accurately detected all thrombi, regardless of their size, location, and age. Although thrombus signal intensity after injection decreased with thrombus age (P<0.001), enhancement at 8 weeks was still present. Gd-DTPA injection was not associated with an improvement of thrombus detection. EP-2104R was superior to both NCE and Gd-DTPA injection (P<0.001). Histopathologic examination showed thrombus organization over time. Fibrin was gradually replaced by fibrous tissue. A strong correlation was found between thrombus enhancement and collagen content of the organizing thrombus with time (R=-0.89; P<0.001). CONCLUSIONS: In an experimental animal model of carotid thrombosis, we have demonstrated the superiority of a fibrin-targeted MR contrast agent for in vivo detection of chronic or organized thrombus, compared with NCE MRI and Gd-DTPA injection.

Animals↗
PubMed2005

Effectiveness of the stent pull-back technique for nonaorto ostial coronary narrowings.

Coronary stenting of nonaorto ostial coronary lesions is challenging because of plaque shift into the main vessel, triggering the use of additional stents. Furthermore, inappropriate coverage of the ostium of the side branch increases the risk of restenosis and target vessel revascularization (TVR). To improve the treatment of nonaorto ostial coronary lesions with a novel interventional technique, we tested the hypothesis that inflating a balloon in the main vessel before stenting the side branch (stent pull-back technique) will limit plaque shifting and reduce the use of additional stents. In addition, proper coverage of the side branch ostium may also reduce 8-month TVR. A case-control design with 100 consecutive patients who underwent drug-eluting stent placement was performed; 55 patients were treated with the stent pull-back technique and 45 patients with a conventional stent technique. Procedural success was 100% for the 2 techniques. The use of additional stents was reduced in the stent pull-back group compared with the conventional stent group (2% vs 18%, p = 0.007). A tendency toward lower ostial miss was also observed in the stent pull-back group (4% vs 13%, p = 0.11). The incidence of in-hospital and 30-day cardiac events was similar between the 2 groups. TVR was lower in the stent pull-back group compared with the conventional group (5% vs 20%; p = 0.03). In conclusion, the stent pull-back technique improves the percutaneous treatment of nonaorto ostial coronary lesions. The technique is associated with a lower use of additional stents and improved clinical outcome, reducing TVR at 8 months of follow-up.

Case-Control Studies↗
PubMed2005

Results of repeat balloon valvuloplasty for treatment of aortic stenosis in patients aged 59 to 104 years.

Balloon aortic valvuloplasty (BAV) may be considered a palliative procedure that is performed in patients who have severely symptomatic aortic stenosis and a prohibitive surgical risk. However, due to poor early survival rates, most previous studies have involved a single BAV procedure. We analyzed long-term outcomes in patients who had severe aortic stenosis and BAV that incorporated repeat procedures to maintain symptom relief and increase survival rate. We retrospectively analyzed 212 consecutive nonsurgical patients (59 to 104 years old) who had severe calcific aortic stenosis and underwent 282 cumulative BAV procedures. Demographic, procedural, and follow-up mortality data were collected. BAV was performed with single or incremental balloon dilatation to obtain a postprocedural transaortic gradient close to 1/3 of the baseline gradient. Peak transaortic gradient after BAV decreased from 55 +/- 22 to 20 +/- 11 mm Hg and aortic valve area increased from 0.6 +/- 0.2 to 1.2 +/- 0.3 cm(2). Mean follow-up duration was 32 +/- 18 months. During follow-up, 24% of patients underwent a second BAV and 9% of patients underwent a third BAV. Duration of symptom alleviation after the first, second, and third BAV procedures were 18 +/- 3, 15 +/- 4, and 10 +/- 3 months, respectively. Median survival rate after BAV was 35 months. Survival rates 1, 3, and 5 years after the procedure were 64%, 28%, and 14% respectively. Patients who underwent repeat BAV had higher 3-year survival rates than did patients who underwent 1 BAV (p = 0.01). Therefore, repeat BAV is a viable treatment strategy in nonsurgical patients who have severe calcific aortic stenosis, because it provides a median survival rate of approximately 3 years and maintains clinical improvement.

Age Factors↗
PubMed2005

Endovascular needle injection of cholesteryl linoleate into the arterial wall produces complex vascular lesions identifiable by intravascular ultrasound: early development in a porcine model of vulnerable plaque.

BACKGROUND: We attempted to create a pig model of complex arterial lesions through the percutaneous injection of cholesteryl linoleate into the vessel wall. METHODS AND RESULTS: A total of 81 arterial segments (27 arteries) underwent percutaneous intramural injection of cholesteryl linoleate, in eight pigs. Intravascular ultrasound (IVUS) analysis and corresponding histology were obtained for analysis at 2 and 4 weeks after injection. Overall, 18 out of 27 (67%) of the injected arterial segments displayed lesions identifiable by IVUS as an eccentric echolucent zone present within the deeper layer of the lesion. Quantitative IVUS analysis demonstrated that these lesions were non-occlusive (36+/-8% area stenosis), eccentric (eccentricity index, 0.78+/-0.07) and located into positively remodeled vessels (remodeling index, 1.45+/-0.24). By histology, these lesions were eccentric and comprised less than a third of the vessel circumference. Medial thickening and a thickened intima containing lipid droplets and mononuclear cells were consistently found. The presence of lipids or local wall thickening seen by histology colocalized with the presence of echolucent structures seen by IVUS in 65% of the coronary segments and 70% of the iliac segments. CONCLUSIONS: The intramural deposition of cholesteryl linoleate results in the development of complex, lipid-containing inflammatory lesions in less than 4 weeks. These lesions are already identifiable by IVUS at 2 weeks and colocalize with histologic findings. Further development of this model may allow the validation of technologies designed to detect and treat high-risk atherosclerotic lesions.

Animals↗
PubMed2004

New aspects in the pathogenesis of diabetic atherothrombosis.

Diabetes mellitus is increasing worldwide, resulting from the interaction of obesity, inflammation, and hyperglycemia. Activated immunity and cytokine production lead to insulin resistance and other components of the metabolic syndrome, establishing the link between diabetes and atherosclerosis. Hyperglycemia-induced endothelial dysfunction is mediated by increased oxidative stress, a promoter of adventitial inflammation and vasa vasorum neovascularization in experimental models of diabetic atherosclerosis. Recent studies have documented increased inflammation, neovascularization, and intraplaque hemorrhage in human diabetic atherosclerosis. This inflammatory microangiopathic process is independently associated with plaque rupture, leading to coronary thrombosis. Tissue factor, the most potent trigger of the coagulation cascade, is increased in diabetic patients with poor glycemic control. Circulating tissue factor microparticles are also associated with apoptosis of plaque macrophages, closing the link among inflammation, plaque rupture, and blood thrombogenicity. High-density lipoproteins, responsible for free cholesterol removal, are reduced in patients with insulin resistance and diabetes. High-density lipoprotein therapy leads to a significant decrease in plaque macrophages and increase in smooth-muscle cells. These beneficial effects may be responsible for coronary plaque stabilization in patients treated with recombinant Apolipoprotein A-I Milano/phospholipid complex. Finally, peroxisomal proliferator-activated receptors (PPARs) are now considered the nuclear transcriptional regulators of atherosclerosis. Three subfamilies, including PPAR-alpha, -delta, and -gamma, have been identified with crucial roles in lipid metabolism, plaque inflammation, expression of adhesion molecules and cytokines, and regulation of matrix metalloproteinases. Multiple experimental studies have documented plaque stabilization with PPAR-gamma agonists, a group of medications holding great promise in the treatment of diabetes atherosclerosis.

Arteriosclerosis↗
PubMed2004

Plaque neovascularization is increased in ruptured atherosclerotic lesions of human aorta: implications for plaque vulnerability.

BACKGROUND: Growth of atherosclerotic plaques is accompanied by neovascularization from vasa vasorum microvessels extending through the tunica media into the base of the plaque and by lumen-derived microvessels through the fibrous cap. Microvessels are associated with plaque hemorrhage and may play a role in plaque rupture. Accordingly, we tested this hypothesis by investigating whether microvessels in the tunica media, the base of the plaque, and the fibrous cap are increased in ruptured atherosclerotic plaques in human aorta. METHODS AND RESULTS: Microvessels, defined as CD34-positive tubuloluminal capillaries recognized in cross-sectional and longitudinal profiles, were quantified in 269 advanced human plaques by bicolor immunohistochemistry. Macrophages/T lymphocytes and smooth muscle cells were defined as CD68/CD3-positive and alpha-actin-positive cells. Total microvessel density was increased in ruptured plaques when compared with nonruptured plaques (P=0.0001). Furthermore, microvessel density was increased in lesions with severe macrophage infiltration at the fibrous cap (P=0.0001) and at the shoulders of the plaque (P=0.0001). In addition, microvessel density was also increased in lesions with intraplaque hemorrhage (P=0.04) and in thin-cap fibroatheromas (P=0.038). Logistic regression analysis identified plaque base microvessel density (P=0.003) as an independent correlate to plaque rupture. CONCLUSIONS: Thus, neovascularization as manifested by the localized appearance of microvessels is increased in ruptured plaques in the human aorta. Furthermore, microvessel density is increased in lesions with inflammation, with intraplaque hemorrhage, and in thin-cap fibroatheromas. Microvessels at the base of the plaque are independently correlated with plaque rupture, suggesting a contributory role for neovascularization in the process of plaque rupture.

Adult↗
PubMed2004

Terminology for high-risk and vulnerable coronary artery plaques. Report of a meeting on the vulnerable plaque, June 17 and 18, 2003, Santorini, Greece.

A group of investigators met for two days in Santorini, Greece, to discuss progress in the field of identification and treatment of high risk/vulnerable atherosclerotic plaques and patients. Many differences in the manner in which terms are being utilized were noted. It was recognized that increased understanding of the pathophysiology of coronary thrombosis and onset of acute coronary syndromes has created the need for agreement on nomenclature. The participants spent considerable time discussing the topic and reached agreement on their own usage of the terms as described below. It is the hope that this usage might be of value to the larger community of scientists working in this field, and that widespread adoption of a common nomenclature would accelerate progress in the prevention of acute coronary events.

Calcinosis↗
PubMed2003

Detection of high-risk atherosclerotic coronary plaques by intravascular spectroscopy.

Multiple technologies are under development to identify plaque composition and vulnerability. This review article is intended to provide basic knowledge to the interventional cardiologist and the clinician about spectroscopy. The concept of light, the wavelength unit and the electromagnetic spectrum are discussed. Different types of spectra analysis including nuclear magnetic resonance, Raman, fluorescence and diffuse reflectance near-infrared spectroscopy are then carefully reviewed. Experimental data to identify atherosclerotic plaque composition for each of these techniques is provided. Potential benefits and challenges are addressed. Finally, diffuse reflectance near-infrared spectroscopy is discussed in more detail as a promising technique to characterize plaque vulnerability in humans.

Coronary Artery Disease↗
PubMed2002

Intimomedial interface damage and adventitial inflammation is increased beneath disrupted atherosclerosis in the aorta: implications for plaque vulnerability.

BACKGROUND: Atherosclerotic plaque progression is frequently accompanied by compensatory enlargement to preserve the lumen. These enlarging plaques develop features of vulnerability, however, leading to disruption and lumen obstruction. This complex transition from compensatory expansion to plaque disruption may not derive solely from progressive intimal disease. Concurrent changes at the intimomedial interface and within the tunica media and adventitia may play a role in plaque instability. We tested this hypothesis by investigating whether interface changes, including internal elastic lamina (IEL) rupture, and medial and adventitial changes, including inflammation, fibrosis, and atrophy, more frequently accompany disrupted than nondisrupted atherosclerotic plaques. METHODS AND RESULTS: Computerized planimetry and ocular micrometry were used for systematic quantification of intimal, medial, and adventitial histopathological features in 598 human aortic plaques according to the AHA classification. Disrupted plaques exhibited larger plaque and lipid pool areas (P=0.0001) and a higher incidence of rupture of the IEL (P=0.0001). Medial and adventitial inflammation (P=0.01), medial fibrosis (P=0.0001), and medial atrophy (P=0.0001) were also higher in disrupted plaques. Furthermore, medial thickness was reduced in disrupted plaques (P=0.0001). Logistic regression analysis identified rupture of the IEL as an independent predictor for fibrous cap disruption (P=0.0001). CONCLUSIONS: Compared with nondisrupted plaques, disrupted plaques have an increased incidence of IEL rupture, medial and adventitial inflammation, medial fibrosis, and medial atrophy. These intimomedial interface and adventitial changes may play a role in the natural history of complex atherosclerotic lesions. The interaction between medial and adventitial pathology and the intimal atherosclerotic process deserves further investigation.

Aorta, Abdominal↗
PubMed2002

Detection of lipid pool, thin fibrous cap, and inflammatory cells in human aortic atherosclerotic plaques by near-infrared spectroscopy.

BACKGROUND: A method is needed to identify nonstenotic, lipid-rich coronary plaques that are likely to cause acute coronary events. Near-infrared (NIR) spectroscopy can provide information on the chemical composition of tissue. We tested the hypothesis that NIR spectroscopy can identify plaque composition and features associated with plaque vulnerability in human aortic atherosclerotic plaques obtained at the time of autopsy. METHODS AND RESULTS: A total of 199 samples from 5 human aortic specimens were analyzed by NIR spectroscopy. Features of plaque vulnerability were defined by histology as presence of lipid pool, thin fibrous cap (<65 microm by ocular micrometry), and inflammatory cell infiltration. An InfraAlyzer 500 spectrophotometer was used. Spectral absorbance values were obtained as log (1/R) data from 1100 to 2200 nm at 10-nm intervals. Principal component regression was used for analysis. An algorithm was constructed with 50% of the samples used as a reference set; blinded predictions of plaque composition were then performed on the remaining samples. NIR spectroscopy sensitivity and specificity for histological features of plaque vulnerability were 90% and 93% for lipid pool, 77% and 93% for thin cap, and 84% and 89% for inflammatory cells, respectively. CONCLUSIONS: NIR spectroscopy can identify plaque composition and features associated with plaque vulnerability in postmortem human aortic specimens. These results support efforts to develop an NIR spectroscopy catheter system to detect vulnerable coronary plaques in living patients.

Algorithms↗