Eric Rhéaume | Université de Montréal (original) (raw)
Papers by Eric Rhéaume
Blood
Background: CD34+ progenitor cells are growingly used for vascular repair. However, in diabetic i... more Background: CD34+ progenitor cells are growingly used for vascular repair. However, in diabetic individuals with cardiovascular diseases, these cells have dysfunctional engraftment capabilities, which compromise their use for autologous cell therapy. The thrombospondin-1-derived peptide RFYVVMWK has previously been reported to stimulate cell adhesiveness through CD47 and integrin activation pathways. Objectives: Our aim was to test whether RFYVVMWK preconditioning could modulate CD34+ cells phenotype and enhance its pro-adhesive properties in diabetic patients. Patients/methods: Peripheral blood mononuclear CD34+ cells isolated from 40 atherosclerotic patients with (TIID; n=20) or without (NonTIID; n=20) type II diabetes were pre-conditioned with 30µM of RFYVVMWK (or truncated peptide RFYVVM. CD34+ cell adhesion was assessed on a vitronectin-collagen matrix and on a TNFa or IL-1b-stimulated HUVEC monolayers. Adhesion receptors, platelet/CD34+ cell conjugates, and cell viability were...
Journal of the American Heart Association
Background-Macrophage cholesterol efflux to high-density lipoproteins (HDLs) is the first step of... more Background-Macrophage cholesterol efflux to high-density lipoproteins (HDLs) is the first step of reverse cholesterol transport. The cholesterol efflux capacity (CEC) of HDL particles is a protective risk factor for coronary artery disease independent of HDL cholesterol levels. Using a genome-wide association study approach, we aimed to identify pathways that regulate CEC in humans. Methods and Results-We measured CEC in 5293 French Canadians. We tested the genetic association between 4 CEC measures and genotypes at >9 million common autosomal DNA sequence variants. These analyses yielded 10 genome-wide significant signals (P<6.25910 À9) representing 7 loci. Five of these loci harbor genes with important roles in lipid biology (CETP, LIPC, LPL, APOA1/C3/A4/A5, and APOE/C1/C2/C4). Except for the APOE/C1/C2/C4 variant (rs141622900, P nonadjusted =1.0910 À11 ; P adjusted =8.8910 À9), the association signals disappear when correcting for HDL cholesterol and triglyceride levels. The additional 2 significant signals were near the PPP1CB/PLB1 and RBFOX3/ENPP7 genes. In secondary analyses, we considered candidate functional variants for 58 genes implicated in HDL biology, as well as 239 variants associated with blood lipid levels and/or coronary artery disease risk by genome-wide association study. These analyses identified 27 significant CEC associations, implicating 5 additional loci (GCKR, LIPG, PLTP, PPARA, and TRIB1). Conclusions-Our genome-wide association study identified common genetic variation at the APOE/C1/C2/C4 locus as a major determinant of CEC that acts largely independently of HDL cholesterol. We predict that HDL-based therapies aiming at increasing CEC will be modulated by changes in the expression of apolipoproteins in this gene cluster.
Arteriosclerosis, thrombosis, and vascular biology, Jan 8, 2016
The mechanisms underlying the pathogenesis of aortic valve calcification remain unclear. With acc... more The mechanisms underlying the pathogenesis of aortic valve calcification remain unclear. With accumulating evidence demonstrating that valve calcification recapitulates bone development, the crucial roles of noncanonical Wnt ligands WNT5a, WNT5b, and WNT11 in osteogenesis make them critical targets in the study of aortic valve calcification. Using immunohistochemistry, RT-PCR, Western blotting, and tissue culture, we examined the tissue distribution of WNT5a, WNT5b, and WNT11 in noncalcified and calcified aortic valves and their effects on human aortic valve interstitial cells (HAVICs). Only focal strong immunostaining for WNT5a was seen in and around areas of calcification. Abundant immunostaining for WNT5b and WNT11 was seen in inflammatory cells, fibrosis, and activated myofibroblasts in areas of calcified foci. There was significant correlation between WNT5b and WNT11 overall staining and presence of calcification, lipid score, fibrosis, and microvessels (P<0.05). RT-PCR and ...
PloS one, 2017
High-density lipoproteins (HDL) favorably affect endothelial progenitor cells (EPC). Circulating ... more High-density lipoproteins (HDL) favorably affect endothelial progenitor cells (EPC). Circulating progenitor cell level and function are impaired in patients with acute coronary syndrome (ACS). This study investigates the short-term effects of reconstituted HDL (rHDL) on circulating progenitor cells in patients with ACS. The study population consisted of 33 patients with recent ACS: 20 patients from the ERASE trial (randomized to receive 4 weekly intravenous infusions of CSL-111 40 mg/kg or placebo) and 13 additional patients recruited as controls using the same enrolment criteria. Blood was collected from 16 rHDL (CSL-111)-treated patients and 17 controls at baseline and at 6-7 weeks (i.e. 2-3 weeks after the fourth infusion of CSL-111 in ERASE). CD34+ and CD34+/kinase insert domain receptor (KDR+) progenitor cell counts were analyzed by flow cytometry. We found preserved CD34+ cell counts in CSL-111-treated subjects at follow-up (change of 1.6%), while the number of CD34+ cells was...
International Journal of Cardiology, 2016
High-density lipoprotein (HDL) infusions induce rapid improvement of experimental atherosclerosis... more High-density lipoprotein (HDL) infusions induce rapid improvement of experimental atherosclerosis in rabbits but their effect on ventricular function remains unknown. We aimed to evaluate the effects of the HDL mimetic peptide CER-522 on left ventricular diastolic dysfunction (LVDD). Rabbits were fed with a cholesterol- and vitamin D2-enriched diet until mild aortic valve stenosis and hypercholesterolemia-induced LV hypertrophy and LVDD developed. Animals then received saline or 10 or 30mg/kg CER-522 infusions 6 times over 2weeks. We performed serial echocardiograms and LV histology to evaluate the effects of CER-522 therapy on LVDD. LVDD was reduced by CER-522 as shown by multiple parameters including early filling mitral deceleration time, deceleration rate, Em/Am ratio, E/Em ratio, pulmonary venous velocities, and LVDD score. These findings were associated with reduced macrophages (RAM-11 positive cells) in the pericoronary area and LV, and decreased levels of apoptotic cardiomyocytes in CER-522-treated rabbits. CER-522 treatment also resulted in decreased atheromatous plaques and internal elastic lamina area in coronary arteries. CER-522 improves LVDD in rabbits, with reductions of LV macrophage accumulation, cardiomyocyte apoptosis, coronary atherosclerosis and remodelling.
International Journal of Cardiology, 2015
The transformation of A5-3f3-hydroxysteroids into the corresponding A4-3-keto-steroids is an esse... more The transformation of A5-3f3-hydroxysteroids into the corresponding A4-3-keto-steroids is an essential step for the biosynthesis of all classes of active steroids: progesterone, mineralocorticoids, glucocorticoids, androgens, and estrogens. These steroid hormones play a crucial role in the differentiation, development, growth, and physiological function of most human tissues. The structures of several cDNAs encoding 3~-HSD isoenzymes have been characterized in human and several other vertebrate species: human types I and H; macaque; bovine; rat types I, H, I11, and IV; mouse types I, H, III, IV, V, and VI; hamster types 1, H, and III; and rainbow trout. Their transient expression reveals that 3fS-HSD and &5-A4-isomerase activities reside within a single protein. Distinct approaches have been used for a better understanding of the structure-function relationships of these 3fS-HSD enzymes: i) affinity radiolabeling studies of the human type I 3~-HSD; ii) identification and the functional consequences of the human type-ll 3[5-HSD mutations detected in patients with 3fS-HSD deficiency. Taken together, all of these data were examined to determine whether the relationship between the genotype and the phenotype of these patients were consistent with in vitro mutagenesis studies. 3fS-HSD deficiency, transmitted in an autosomic recessive disorder, is characterized by varying degrees of salt wasting; in genetic males, fetal testicular 3~3-HSD deficiency causes an undervirilized male genitalia (male pseudohermaphroditism); females exhibit either normal sexual differentiation or mild virilization. All mutations were detected in the type H 3 ~-HSD gene, which is expressed almost exclusively in the adrenals and gonads. No mutation was detected in the type 1 3f3-HSD gene, which is expressed in peripheral tissues. The finding of a normal type 1 3fS-HSD gene explains the elevated A5-steroids and mild virilization of affected girls at birth. To date, 24 mutations have been identified in 25 distinct families with 3~-HSD deficiencies. All nonsense and frameshift mutations introducing a premature termination codon were associated with the classical salt-losing form. The locations of these nonsense mutations suggest that at least the first 318 amino acids out of 371 are required for 3fS-HSD activity. The consequences of the missense mutations on some domains of the 3f3-enzyme, such as membrane-spanning domains, cofactorbinding site, and steroid-binding site, were reviewed. The future crystallization of the overexpressed normal and mutant-type H-3~-HSD enzymes should contribute to a better understanding of the structure-function relationships of this enzyme, especially for missense mutations located outside the putative functional regions.
Annals of the New York Academy of Sciences, 1984
Biomedical Optics Express, 2014
Combining Fluorescent Molecular Tomography (FMT) with anatomical imaging, e.g. MRI facilitates in... more Combining Fluorescent Molecular Tomography (FMT) with anatomical imaging, e.g. MRI facilitates interpreting functional information. Furthermore, using a heterogeneous model for light propagation has been shown in simulations to be superior to homogeneous modeling to quantify fluorescence. Here, we present a combined FMT-MRI system and apply it to heart and aorta molecular imaging, a challenging area due to strong tissue heterogeneity and the presence of air-voids due to lungs. First investigating performance in a phantom and mouse corpse, the MRI-enabled heterogeneous models resulted in an improved quantification of fluorescence reconstructions. The system was then used in mice for in vivo atherosclerosis molecular imaging. Results show that, when using the heterogeneous model, reconstructions were in agreement with the ex vivo measurements. Therefore, the proposed system might serve as a powerful imaging tool for atherosclerosis in mice.
Journal of Biomedical Optics, 2011
In this paper, we present a dual-modality imaging system combining three-dimensional (3D) continu... more In this paper, we present a dual-modality imaging system combining three-dimensional (3D) continuouswave transillumination fluorescence tomography with 3D ultrasound (US) imaging. We validated the system with two phantoms, one containing fluorescent inclusions (Cy5.5) at different depths, and another varying-thickness semicylindrical phantom. Using raster scanning, the combined fluorescence/US system was used to collect the boundary fluorescent emission in the X-Y plane, as well as recovered the 3D surface and position of the inclusions from US signals. US images were segmented to provide soft priors for the fluorescence image reconstruction. Phantom results demonstrated that with priors derived from the US images, the fluorescent reconstruction quality was significantly improved. As further evaluation, we show pilot in vivo results using an Apo-E mouse to assess the feasibility and performance of this system in animal studies. Limitations and potential to be used in artherosclerosis studies are then discussed. C 2011 Society of Photo-Optical Instrumentation Engineers (SPIE).
Canadian Journal of Cardiology, 2011
Circulation. Cardiovascular genetics, Jan 11, 2015
Biomedical Optics Express, 2015
Coronary artery disease is characterized by atherosclerotic plaque formation. Despite impressive ... more Coronary artery disease is characterized by atherosclerotic plaque formation. Despite impressive advances in intravascular imaging modalities, in vivo molecular plaque characterization remains challenging, and different multimodality imaging systems have been proposed. We validated an engineered bimodal intravascular ultrasound imaging (IVUS) / near-infrared fluorescence (NIRF) imaging catheter in vivo using a balloon injury atherosclerosis rabbit model. Rabbit aortas and right iliac arteries were scanned in vivo after indocyanine green (ICG) injection, and compared to corresponding ex vivo fluorescence and white light images. Areas of ICG accumulation were colocalized with macroscopic atherosclerotic plaque formation. In vivo imaging was performed with the bimodal catheter integrating ICG-induced fluorescence signals into cross-sectional IVUS imaging. In vivo ICG accumulation corresponded to ex vivo fluorescence signal intensity and IVUS identified plaques.
Molecular Endocrinology
The 3,8-hydroxysteroid dehydrogenase/ .ii 5 -..::i 4 isomerase (3,8HSD) enzyme catalyzes the oxid... more The 3,8-hydroxysteroid dehydrogenase/ .ii 5 -..::i 4 isomerase (3,8HSD) enzyme catalyzes the oxidation and isomerization of .Li 5 -3,8-hydroxysteroid precursors into .Li 4 -ketosteroids, thus leading to the formation of all classes of steroid hormones. In addition, 3,8HSD catalyzes the interconversion of 3,8hydroxy-and 3-keto-5a-androstane steroids. Clinical observations in patients with 3,8HSD deficiency as well as our recent data obtained by Southern blot analysis using a human placental 3,8HSD cDNA (type I) as probe suggested the existence of multiple related 3,8HSD isoenzymes. We now report the isolation and characterization of a second type of cDNA clone (arbitrarily designated type II) encoding 3,8HSD after screening of a human adrenal >.gt22A library. The nucleotide sequence of 1676 basepairs of human 3,8HSD type II cDNA predicts a protein of 371 amino acids with a calculated molecular mass of 41,921 daltons, which displays 93.5% and 96.2% homology with human placental type I and rhesus macaque ovary 3,8HSD deduced proteins, respectively. To characterize and compare the kinetic properties of the two isoenzymes, plasmids derived from pCMV and containing type I or type II 3,8HSD fulllength cDNA inserts were transiently expressed in Hela human cervical carcinoma cells. In vitro incubation with NAO+ and 3 H-labeled pregnenolone or dehydroepiandrosterone shows that the type I protein possesses a 3,BHSD /.Li 5 -..::i 4 isomerase activity higher than type II, with respective Km values of 0.24 vs. 1.2 µM for pregnenolone and 0.18 vs.
NeuroReport, 1992
In order to assess the role of sex steroids on the regulation of neuropeptide Y (NPY), levels of ... more In order to assess the role of sex steroids on the regulation of neuropeptide Y (NPY), levels of pre-proNPY mRNA were measured by in situ hybridization in the rat arcuate nucleus during the estrous cycle. Pre-proNPY mRNA levels were quite stable during diestrus I, diestrus II and the morning of the proestrus, and were 25-30% higher during the afternoon of the proestrus and during the day of the estrus. These data suggest that NPY synthesis is modulated by variations in the circulating levels of sex steroids. Also the excellent correlation between the variations in the levels of pre-proNPY mRNA and those of luteinizing hormone-releasing hormone (LHRH) mRNA observed throughout the estrous cycle supports the hypothesis that NPY might be involved in the regulation of LHRH secretion.
Blood
Background: CD34+ progenitor cells are growingly used for vascular repair. However, in diabetic i... more Background: CD34+ progenitor cells are growingly used for vascular repair. However, in diabetic individuals with cardiovascular diseases, these cells have dysfunctional engraftment capabilities, which compromise their use for autologous cell therapy. The thrombospondin-1-derived peptide RFYVVMWK has previously been reported to stimulate cell adhesiveness through CD47 and integrin activation pathways. Objectives: Our aim was to test whether RFYVVMWK preconditioning could modulate CD34+ cells phenotype and enhance its pro-adhesive properties in diabetic patients. Patients/methods: Peripheral blood mononuclear CD34+ cells isolated from 40 atherosclerotic patients with (TIID; n=20) or without (NonTIID; n=20) type II diabetes were pre-conditioned with 30µM of RFYVVMWK (or truncated peptide RFYVVM. CD34+ cell adhesion was assessed on a vitronectin-collagen matrix and on a TNFa or IL-1b-stimulated HUVEC monolayers. Adhesion receptors, platelet/CD34+ cell conjugates, and cell viability were...
Journal of the American Heart Association
Background-Macrophage cholesterol efflux to high-density lipoproteins (HDLs) is the first step of... more Background-Macrophage cholesterol efflux to high-density lipoproteins (HDLs) is the first step of reverse cholesterol transport. The cholesterol efflux capacity (CEC) of HDL particles is a protective risk factor for coronary artery disease independent of HDL cholesterol levels. Using a genome-wide association study approach, we aimed to identify pathways that regulate CEC in humans. Methods and Results-We measured CEC in 5293 French Canadians. We tested the genetic association between 4 CEC measures and genotypes at >9 million common autosomal DNA sequence variants. These analyses yielded 10 genome-wide significant signals (P<6.25910 À9) representing 7 loci. Five of these loci harbor genes with important roles in lipid biology (CETP, LIPC, LPL, APOA1/C3/A4/A5, and APOE/C1/C2/C4). Except for the APOE/C1/C2/C4 variant (rs141622900, P nonadjusted =1.0910 À11 ; P adjusted =8.8910 À9), the association signals disappear when correcting for HDL cholesterol and triglyceride levels. The additional 2 significant signals were near the PPP1CB/PLB1 and RBFOX3/ENPP7 genes. In secondary analyses, we considered candidate functional variants for 58 genes implicated in HDL biology, as well as 239 variants associated with blood lipid levels and/or coronary artery disease risk by genome-wide association study. These analyses identified 27 significant CEC associations, implicating 5 additional loci (GCKR, LIPG, PLTP, PPARA, and TRIB1). Conclusions-Our genome-wide association study identified common genetic variation at the APOE/C1/C2/C4 locus as a major determinant of CEC that acts largely independently of HDL cholesterol. We predict that HDL-based therapies aiming at increasing CEC will be modulated by changes in the expression of apolipoproteins in this gene cluster.
Arteriosclerosis, thrombosis, and vascular biology, Jan 8, 2016
The mechanisms underlying the pathogenesis of aortic valve calcification remain unclear. With acc... more The mechanisms underlying the pathogenesis of aortic valve calcification remain unclear. With accumulating evidence demonstrating that valve calcification recapitulates bone development, the crucial roles of noncanonical Wnt ligands WNT5a, WNT5b, and WNT11 in osteogenesis make them critical targets in the study of aortic valve calcification. Using immunohistochemistry, RT-PCR, Western blotting, and tissue culture, we examined the tissue distribution of WNT5a, WNT5b, and WNT11 in noncalcified and calcified aortic valves and their effects on human aortic valve interstitial cells (HAVICs). Only focal strong immunostaining for WNT5a was seen in and around areas of calcification. Abundant immunostaining for WNT5b and WNT11 was seen in inflammatory cells, fibrosis, and activated myofibroblasts in areas of calcified foci. There was significant correlation between WNT5b and WNT11 overall staining and presence of calcification, lipid score, fibrosis, and microvessels (P<0.05). RT-PCR and ...
PloS one, 2017
High-density lipoproteins (HDL) favorably affect endothelial progenitor cells (EPC). Circulating ... more High-density lipoproteins (HDL) favorably affect endothelial progenitor cells (EPC). Circulating progenitor cell level and function are impaired in patients with acute coronary syndrome (ACS). This study investigates the short-term effects of reconstituted HDL (rHDL) on circulating progenitor cells in patients with ACS. The study population consisted of 33 patients with recent ACS: 20 patients from the ERASE trial (randomized to receive 4 weekly intravenous infusions of CSL-111 40 mg/kg or placebo) and 13 additional patients recruited as controls using the same enrolment criteria. Blood was collected from 16 rHDL (CSL-111)-treated patients and 17 controls at baseline and at 6-7 weeks (i.e. 2-3 weeks after the fourth infusion of CSL-111 in ERASE). CD34+ and CD34+/kinase insert domain receptor (KDR+) progenitor cell counts were analyzed by flow cytometry. We found preserved CD34+ cell counts in CSL-111-treated subjects at follow-up (change of 1.6%), while the number of CD34+ cells was...
International Journal of Cardiology, 2016
High-density lipoprotein (HDL) infusions induce rapid improvement of experimental atherosclerosis... more High-density lipoprotein (HDL) infusions induce rapid improvement of experimental atherosclerosis in rabbits but their effect on ventricular function remains unknown. We aimed to evaluate the effects of the HDL mimetic peptide CER-522 on left ventricular diastolic dysfunction (LVDD). Rabbits were fed with a cholesterol- and vitamin D2-enriched diet until mild aortic valve stenosis and hypercholesterolemia-induced LV hypertrophy and LVDD developed. Animals then received saline or 10 or 30mg/kg CER-522 infusions 6 times over 2weeks. We performed serial echocardiograms and LV histology to evaluate the effects of CER-522 therapy on LVDD. LVDD was reduced by CER-522 as shown by multiple parameters including early filling mitral deceleration time, deceleration rate, Em/Am ratio, E/Em ratio, pulmonary venous velocities, and LVDD score. These findings were associated with reduced macrophages (RAM-11 positive cells) in the pericoronary area and LV, and decreased levels of apoptotic cardiomyocytes in CER-522-treated rabbits. CER-522 treatment also resulted in decreased atheromatous plaques and internal elastic lamina area in coronary arteries. CER-522 improves LVDD in rabbits, with reductions of LV macrophage accumulation, cardiomyocyte apoptosis, coronary atherosclerosis and remodelling.
International Journal of Cardiology, 2015
The transformation of A5-3f3-hydroxysteroids into the corresponding A4-3-keto-steroids is an esse... more The transformation of A5-3f3-hydroxysteroids into the corresponding A4-3-keto-steroids is an essential step for the biosynthesis of all classes of active steroids: progesterone, mineralocorticoids, glucocorticoids, androgens, and estrogens. These steroid hormones play a crucial role in the differentiation, development, growth, and physiological function of most human tissues. The structures of several cDNAs encoding 3~-HSD isoenzymes have been characterized in human and several other vertebrate species: human types I and H; macaque; bovine; rat types I, H, I11, and IV; mouse types I, H, III, IV, V, and VI; hamster types 1, H, and III; and rainbow trout. Their transient expression reveals that 3fS-HSD and &5-A4-isomerase activities reside within a single protein. Distinct approaches have been used for a better understanding of the structure-function relationships of these 3fS-HSD enzymes: i) affinity radiolabeling studies of the human type I 3~-HSD; ii) identification and the functional consequences of the human type-ll 3[5-HSD mutations detected in patients with 3fS-HSD deficiency. Taken together, all of these data were examined to determine whether the relationship between the genotype and the phenotype of these patients were consistent with in vitro mutagenesis studies. 3fS-HSD deficiency, transmitted in an autosomic recessive disorder, is characterized by varying degrees of salt wasting; in genetic males, fetal testicular 3~3-HSD deficiency causes an undervirilized male genitalia (male pseudohermaphroditism); females exhibit either normal sexual differentiation or mild virilization. All mutations were detected in the type H 3 ~-HSD gene, which is expressed almost exclusively in the adrenals and gonads. No mutation was detected in the type 1 3f3-HSD gene, which is expressed in peripheral tissues. The finding of a normal type 1 3fS-HSD gene explains the elevated A5-steroids and mild virilization of affected girls at birth. To date, 24 mutations have been identified in 25 distinct families with 3~-HSD deficiencies. All nonsense and frameshift mutations introducing a premature termination codon were associated with the classical salt-losing form. The locations of these nonsense mutations suggest that at least the first 318 amino acids out of 371 are required for 3fS-HSD activity. The consequences of the missense mutations on some domains of the 3f3-enzyme, such as membrane-spanning domains, cofactorbinding site, and steroid-binding site, were reviewed. The future crystallization of the overexpressed normal and mutant-type H-3~-HSD enzymes should contribute to a better understanding of the structure-function relationships of this enzyme, especially for missense mutations located outside the putative functional regions.
Annals of the New York Academy of Sciences, 1984
Biomedical Optics Express, 2014
Combining Fluorescent Molecular Tomography (FMT) with anatomical imaging, e.g. MRI facilitates in... more Combining Fluorescent Molecular Tomography (FMT) with anatomical imaging, e.g. MRI facilitates interpreting functional information. Furthermore, using a heterogeneous model for light propagation has been shown in simulations to be superior to homogeneous modeling to quantify fluorescence. Here, we present a combined FMT-MRI system and apply it to heart and aorta molecular imaging, a challenging area due to strong tissue heterogeneity and the presence of air-voids due to lungs. First investigating performance in a phantom and mouse corpse, the MRI-enabled heterogeneous models resulted in an improved quantification of fluorescence reconstructions. The system was then used in mice for in vivo atherosclerosis molecular imaging. Results show that, when using the heterogeneous model, reconstructions were in agreement with the ex vivo measurements. Therefore, the proposed system might serve as a powerful imaging tool for atherosclerosis in mice.
Journal of Biomedical Optics, 2011
In this paper, we present a dual-modality imaging system combining three-dimensional (3D) continu... more In this paper, we present a dual-modality imaging system combining three-dimensional (3D) continuouswave transillumination fluorescence tomography with 3D ultrasound (US) imaging. We validated the system with two phantoms, one containing fluorescent inclusions (Cy5.5) at different depths, and another varying-thickness semicylindrical phantom. Using raster scanning, the combined fluorescence/US system was used to collect the boundary fluorescent emission in the X-Y plane, as well as recovered the 3D surface and position of the inclusions from US signals. US images were segmented to provide soft priors for the fluorescence image reconstruction. Phantom results demonstrated that with priors derived from the US images, the fluorescent reconstruction quality was significantly improved. As further evaluation, we show pilot in vivo results using an Apo-E mouse to assess the feasibility and performance of this system in animal studies. Limitations and potential to be used in artherosclerosis studies are then discussed. C 2011 Society of Photo-Optical Instrumentation Engineers (SPIE).
Canadian Journal of Cardiology, 2011
Circulation. Cardiovascular genetics, Jan 11, 2015
Biomedical Optics Express, 2015
Coronary artery disease is characterized by atherosclerotic plaque formation. Despite impressive ... more Coronary artery disease is characterized by atherosclerotic plaque formation. Despite impressive advances in intravascular imaging modalities, in vivo molecular plaque characterization remains challenging, and different multimodality imaging systems have been proposed. We validated an engineered bimodal intravascular ultrasound imaging (IVUS) / near-infrared fluorescence (NIRF) imaging catheter in vivo using a balloon injury atherosclerosis rabbit model. Rabbit aortas and right iliac arteries were scanned in vivo after indocyanine green (ICG) injection, and compared to corresponding ex vivo fluorescence and white light images. Areas of ICG accumulation were colocalized with macroscopic atherosclerotic plaque formation. In vivo imaging was performed with the bimodal catheter integrating ICG-induced fluorescence signals into cross-sectional IVUS imaging. In vivo ICG accumulation corresponded to ex vivo fluorescence signal intensity and IVUS identified plaques.
Molecular Endocrinology
The 3,8-hydroxysteroid dehydrogenase/ .ii 5 -..::i 4 isomerase (3,8HSD) enzyme catalyzes the oxid... more The 3,8-hydroxysteroid dehydrogenase/ .ii 5 -..::i 4 isomerase (3,8HSD) enzyme catalyzes the oxidation and isomerization of .Li 5 -3,8-hydroxysteroid precursors into .Li 4 -ketosteroids, thus leading to the formation of all classes of steroid hormones. In addition, 3,8HSD catalyzes the interconversion of 3,8hydroxy-and 3-keto-5a-androstane steroids. Clinical observations in patients with 3,8HSD deficiency as well as our recent data obtained by Southern blot analysis using a human placental 3,8HSD cDNA (type I) as probe suggested the existence of multiple related 3,8HSD isoenzymes. We now report the isolation and characterization of a second type of cDNA clone (arbitrarily designated type II) encoding 3,8HSD after screening of a human adrenal >.gt22A library. The nucleotide sequence of 1676 basepairs of human 3,8HSD type II cDNA predicts a protein of 371 amino acids with a calculated molecular mass of 41,921 daltons, which displays 93.5% and 96.2% homology with human placental type I and rhesus macaque ovary 3,8HSD deduced proteins, respectively. To characterize and compare the kinetic properties of the two isoenzymes, plasmids derived from pCMV and containing type I or type II 3,8HSD fulllength cDNA inserts were transiently expressed in Hela human cervical carcinoma cells. In vitro incubation with NAO+ and 3 H-labeled pregnenolone or dehydroepiandrosterone shows that the type I protein possesses a 3,BHSD /.Li 5 -..::i 4 isomerase activity higher than type II, with respective Km values of 0.24 vs. 1.2 µM for pregnenolone and 0.18 vs.
NeuroReport, 1992
In order to assess the role of sex steroids on the regulation of neuropeptide Y (NPY), levels of ... more In order to assess the role of sex steroids on the regulation of neuropeptide Y (NPY), levels of pre-proNPY mRNA were measured by in situ hybridization in the rat arcuate nucleus during the estrous cycle. Pre-proNPY mRNA levels were quite stable during diestrus I, diestrus II and the morning of the proestrus, and were 25-30% higher during the afternoon of the proestrus and during the day of the estrus. These data suggest that NPY synthesis is modulated by variations in the circulating levels of sex steroids. Also the excellent correlation between the variations in the levels of pre-proNPY mRNA and those of luteinizing hormone-releasing hormone (LHRH) mRNA observed throughout the estrous cycle supports the hypothesis that NPY might be involved in the regulation of LHRH secretion.