Lukasz Partyka

Regulation of platelet adhesion by oxidized lipoproteins and oxidized phospholipids.

Activated platelets adhere to the endothelium and release vasoactive mediators which induce vasoconstriction and remodeling of the vessel wall. The influence of native and ex vivo oxidized lipoproteins enriched with oxidized 1-palmitoyl-2-arachidonoyl- sn -glycero-3-phosphorylcholine (ox-PAPC), the major lipid responsible for the biological activity of minimally oxidized LDL (mm-LDL), on platelet adhesion, membrane receptor expression and aggregation was studied. Influence of native and oxidized lipoproteins (5-100 w g protein/ml); ox-PAPC (0.5-50 w g/ml); ADP (1-10 w M) as well as the specific phosphatase 1 and 2A inhibitor okadaic acid (3-10 w M) on platelet adhesion, receptor expression and aggregation was measured. Platelets adhered to all the classes of lipoproteins immobilized in plastic microtiter wells (native lipoproteins: HDL<LDL<VLDL<oxidized lipoproteins<ox-PAPC-enriched lipoproteins). Flow cytometry revealed that lipoproteins increased CD41 expression. Preincubation of platelets with ox-PAPC alone, significantly up-regulated CD62p and CD41 receptors (higher dose) but potently inhibited anti-CD36 MoAb binding. Okadaic acid increased anti-CD41 and decreased anti-CD36 and anti-CD42b MoAbs binding. Neither ox-PAPC nor okadaic acid induced platelet aggregation. CD36 seems to be the main receptor responsible for binding of oxidized lipoproteins, particularly its ox-PAPC epitope. The effect of okadaic acid on CD36 and CD41 argue for the participation of phosphorylation-dependent reorganization of cellular trafficking and microtubule organization by ox-PAPC.

Virtual Histology-Intravascular Ultrasound Assessment of Lesion Coverage After Angiographically-Guided Stent Implantation in Patients With ST Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention

An occlusion or severe stenosis (angiographic culprit lesion) of the infarct-related artery is frequently located at the site of the maximum thrombus burden, whereas the origin of the plaque rupture (the true culprit) can be situated proximal or distal to it. The aim of this study was to examine stent coverage of true culprit lesions in 20 patients who underwent primary percutaneous coronary intervention and had Thrombolysis In Myocardial Infarction (TIMI) grade 3 flow restored in the infarct-related artery by angiographically guided direct stenting. Images of lesions were obtained using virtual histology-intravascular ultrasound before and after intervention (blinded to the operator). Plaque rupture sites were identified by intravascular ultrasound in 12 lesions (60%), 11 proximal and 1 distal to the minimum luminal area (MLA). Maximum necrotic core sites were found proximal to the MLA in 16 lesions, at the MLA in 3 lesions, and distal to the MLA in 1 lesion. Plaque rupture sites were fully covered by stents in 11 lesions. Virtual histology-intravascular ultrasound-derived thin-cap fibroatheroma longitudinal geographic misses were found in 10 lesions, 7 in the proximal reference segment and in 3 patients in the proximal and distal reference segments. In conclusion, in about 50% of patients who undergo primary percutaneous coronary intervention for ST-segment elevation myocardial infarction with optimal angiographic results, the stent does not fully cover the maximum necrotic core site related to the culprit lesion.

The effect of the plasma n-3/n-6 polyunsaturated fatty acid ratio on the dietary LDL phenotype transformation – Insights from the LIPGENE study

BACKGROUND & AIMS LDL phenotype B is associated with obesity, insulin resistance, hypertriglyceridemia and oxidative stress. The effect of plasma n-3/n-6 PUFA ratio on LDL phenotype transformation was investigated. METHODS Patients with metabolic syndrome (n=99) received one of four isocaloric diets: (A) High-fat (38% energy) SFA-rich diet (HSFA); (B) High-fat (38% energy), MUFA-rich diet (HMUFA); (C), low-fat (LF) (28% energy), high-complex carbohydrate diet with 1.24g/d oleic sunflower oil (LFHCC) and (D): low-fat (28% energy), high-complex carbohydrate diet, with 1.24g/d LC n-3 PUFA (LFHCC n-3) for 12 weeks. Analysis of plasma lipid profile and LDL phenotype was done pre- and post-interventions. RESULTS Post-dietary change of LDL density was a main effect observed in all groups. LFHCC n-3 and HFMUFA diets resulted in favorable alteration of LDL phenotype from B to A and decreased LDL density. In contrast, increased LDL density was observed in HSFA and LFHCC groups. The plasma pre-n3/n6 PUFA, Apo E change and pre-Apo CIII/CII ratios explained in 65% the post-dietary change of LDL density in diet LFHCC n-3 consumers. CONCLUSIONS Study demonstrates efficacy of dietary n-3 PUFA to modify pro-atherogenic to less atherogenic LDL phenotype in patients with metabolic syndrome. Study identifier at ClinicalTrials.gov was NCT00429195.

Analysis of candidate genes in Polish families with obesity.

Abstract This study analyzes the relationship between risk factors related to overweight/obesity, insulin resistance, lipid tolerance, hypertension, endothelial function and genetic polymorphisms associated with: i) appetite regulation (leptin, melanocortin-3-receptor (MCR-3), dopamine receptor 2 (D2R)); ii) adipocyte differentiation and insulin sensitivity (peroxisome proliferator-activated receptor-γ2 (PPAR-γ2), tumor necrosis factor-α (TNF-α)); iii) thermogenesis and free fatty acid (FFA) transport/catabolism (uncoupling protein-1 (UCP1), lipoprotein lipase (LPL), β2- and β3-adrenergic receptor (β2AR, β3AR), fatty acid transport protein-1 (FATP-1) and iv) lipoproteins (apoliprotein E (apoE), apo CIII). The 122 members of 40 obese Caucasian families from southern Poland participated in the study. The genotypes were analyzed by restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) or by direct sequencing. Phenotypes related to obesity (body mass index (BMI), fat/lean body mass composition, waist-to-hip ratio (WHR)), fasting lipids, glucose, leptin and insulin, as well as insulin during oral glucose tolerance test (OGTT) (4 points within 2 hours) and during oral lipid tolerance test (OLTT) (5 points within 8 hours) were assessed. The insulin sensitivity indexes: homeostasis model assessment of insulin resistance, whole body insulin sensitivity index, hepatic insulin sensitivity and early secretory response to an oral glucose load (HOMA-IR, ISI-COMP, ISI-HOMA and DELTA) were calculated. The single gene mutations such as C105 T OB and Pro115 Gln PPAR-γ2 linked to morbid obesity were not detected in our group. A weak correlation between obesity and certain gene polymorphisms was observed. Being overweight (25<BMI≤30 kg/m2) significantly correlated with worse FFA tolerance in male PPAR-γ2 12Pro, LPL-H (G) allele carriers. Insulin resistance was found in female PPAR-γ2 Pro12, TNF-α (−308A) and LPL-H (G) allele carriers. Hypertension linked to the PPAR-γ2 Pro allele carriers was characterized by high leptin output during OLTT. We conclude that the polymorphisms we investigated were weakly correlated with obesity but significantly modified the risk factors of the metabolic syndrome.

Induction of Nitric Oxide Synthase (NOS) and Vascular Endothelial Growth Factor (VEGF) in Experimental Model of Angioplasty and Heart Ischemia

Balloon angioplasty (e. g. PTCA) leads to the activation of a number of genes in injured vessels1. As a consequence of the endothelium damage several characteristic reactions, such as thrombus formation, vasoconstriction and finally - vascular smooth muscle cell (VSMC) proliferation, lead to restenosis1. Among other things, the diminished generation of nitric oxide (NO), due to the lack of constitutively expressed endothelial NO synthase (eNOS) is causatively connected with this process.

Effects of Trans-Endocardial Delivery of Bone Marrow-Derived CD133+ Cells on Left Ventricle Perfusion and Function in Patients With Refractory Angina: Final Results of Randomized, Double-Blinded, Placebo-Controlled REGENT-VSEL Trial.

Rationale: New therapies for refractory angina are needed. Objective: Assessment of transendocardial delivery of bone marrow CD133+ cells in patients with refractory angina. Methods and Results: Randomized, double-blinded, placebo-controlled trial enrolled 31 patients with recurrent Canadian Cardiovascular Society II–IV angina, despite optimal medical therapy, ≥1 myocardial segment with inducible ischemia in Tc-99m SPECT who underwent bone marrow biopsy and were allocated to cells (n=16) or placebo (n=15). Primary end point was absolute change in myocardial ischemia by SPECT. Secondary end points were left ventricular function and volumes by magnetic resonance imaging and angina severity. After 4 months, there were no significant differences in extent of inducible ischemia between groups (summed difference score mean [±SD]: 2.60 [2.6] versus 3.63 [3.6], P=0.52; total perfusion deficit: 3.60 [3.6] versus 5.01 [4.3], P=0.32; absolute changes of summed difference score: −1.38 [5.2] versus −0.73 [1.9], P=0.65; and total perfusion deficit: −1.33 [3.3] versus −2.19 [6.6], P=0.65). There was a significant reduction of left ventricular volumes (end-systolic volume: −4.3 [11.3] versus 7.4 [11.8], P=0.02; end-diastolic volume: −9.1 [14.9] versus 7.4 [15.8], P=0.02) and no significant change of left ventricular ejection fraction in the cell group. There was no difference in number of patients showing improvement of ≥1 Canadian Cardiovascular Society class after 1 (41.7% versus 58.3%; P=0.68), 4 (50% versus 33.3%; P=0.63), 6 (70% versus 50.0%; P=0.42), and 12 months (55.6% versus 81.8%; P=0.33) and use of nitrates after 12 months. Conclusion: Transendocardial CD133+ cell therapy was safe. Study was underpowered to conclusively validate the efficacy, but it did not show a significant reduction of myocardial ischemia and angina versus placebo. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01660581.

Evaluation of genetic predisposition to insulin resistance by nutrient-induced insulin output ratio (NIOR).

Abstract Background: New tools to identify genotype-phenotype interactions need to be described and implemented. The aim of this study was to identify correlation between the risk originating from gene variation and diet-dependent development of insulin resistance. Methods: Insulin output in terms of area under the curve after an oral glucose tolerance test (AUC Ins OGTT) and lipid tolerance tests (AUC Ins OLTT) were measured in 167 overweight/obese patients. Estimation of the 18 common gene polymorphisms for obesity risk and standard phenotyping were performed. Results: Insulin output (AUC Ins OGTT) correlated strongly between both insulin treatments across the whole group. However, within the genotype sub-groups, correlation was lower or did not exist. Using a nutrient-induced insulin output ratio (NIOR), calculated as AUC Ins OLTT/AUC Ins OGTT, values ranged from 0.42 to 5.83 and correlated significantly with body mass index (BMI) and leptin, but not with age, gender, waist-to-hip ratio (WHR) and homeostasis model assessment of insulin resistance (HOMA-IR) or plasma adiponectin. High NIOR was found in a subgroup of carriers of rare allelic variants of genes characteristic for poorer tolerance to lipids in the diet. Low NIOR values were found within a sub-group with rare genetic variants regulating carbohydrate metabolism. Thus, the new insulin index NIOR may distinguish gene variant carriers into groups of glucose- or lipid-sensitive phenotypes. Conclusions: We suggest that the OLTT/OGTT insulin output ratio (NIOR) may be predictive for identifying individuals who are phenotypically susceptible to insulin resistance in response to high fat or carbohydrate in their habitual diet. Clin Chem Lab Med 2007;45:1124–32.

An optical coherence tomography study of neointimal morphology and strut coverage at different time intervals from implantation of biodegradable polymer-coated sirolimus-eluting stents

The aim of the study was to capture the evolution of neointima after implantation of a biodegradable polymer–coated, sirolimus–eluting, cobalt–chromium coronary stent system (BP‐DES).

Effects of trans-endocardial delivery of bone marrow-derived CD133+ cells on angina and quality of life in patients with refractory angina: A sub-analysis of the REGENT-VSEL trial

BACKGROUND The REGENT-VSEL trial demonstrated a neutral effect of transendocardial injection of autologous bone marrow (BM)-derived CD133+ in regard to myocardial ischemia. The current sub-analysis of the REGENT VSEL trial aims to assess the effect stem cell therapy has on quality of life (QoL) in patients with refractory angina. METHODS Thirty-one patients (63.0 ± 6.4 years, 70% male) with recurrent CCS II-IV angina, despite optimal medical therapy, enrolled in the REGENT-VSEL single center, randomized, double-blinded, and placebo-controlled trial. Of the 31 patients, 16 individuals were randomly assigned to the active stem cell group and 15 individuals were randomly assigned to the placebo group on a 1:1 basis. The inducibility of ischemia, (≥ one myocardial segment) was confirmed for each patient using Tc-99m SPECT. QoL was measured using the Seattle Angina Questionnaire. Each patient completed the questionnaire prior to treatment and at the time of their outpatient follow-up visits at 1, 4, 6, and 12 months after cell/placebo treatment. RESULTS The main finding of the REGENT-VSEL trial sub-analysis was that transendocardial injection of autologous BM-derived CD133+ stem cells in patients with chronic refractory angina did not show significant improvement in QoL in comparison to the control group. Moreover, there was no significant difference between cell therapy and placebo in a number of patients showing improvement of at least 1 Canadian Cardiovascular Society class during the follow-up period. CONCLUSIONS Intra-myocardial delivery of autologous CD133+ stem cells is safe and feasible but does not show a significant improvement in the QoL or angina pectoris symptoms in patients with chronic myocardial ischemia.

TCT-796 Highly Calcific Carotid Lesions Endovascular Revascularization Using a Novel, Dual-layer Carotid Stent System CGuardTM: Analysis from the PARADIGM Study

TCT-796 Highly Calcific Carotid Lesions Endovascular Revascularization Using a Novel, Dual-layer Carotid Stent System CGuardTM: Analysis from the PARADIGM Study Adam Mazurek, Mariusz Trystuła, Jacek Jąkała, Andrzej Brzychczy, Anna Borraty nska, Agata Le sniak-Sobelga, Małgorzata Urba nczyk, R. Paweł Bany s, Wojciech Zajdel, Klaudia Proniewska, Lukasz Partyka, Krzysztof Zmudka, Piotr Podolec, Piotr Musialek Department od Cardiac and Vascular Diseases, John Paul II ND Hospital, Krakow, Poland; School of Medicine, University of California, Irvine; UC Davis; Kurume-univaersity; John Paul II Hospital, Krakow, Poland; Al Qassimi Hospital; Clinical centre of Serbia; John Paul II Hospital, Krakow, Poland; Clinical Dept. of Interventional Cardiology, John Paul II Hospital, Krakow, Poland; Krakow Cardiovascular Research Institute, Krakow, Poland; University Hospital Krakow, Krakow, Poland; John Paul II Hospital in Krakow, Krakow, Poland; Clinical Center of Serbia; John Paul II Hospital, Krakow, Poland