SlideShare a Scribd company logo

More Related Content

Viewers also liked (10)

Optic
OpticOptic
Optic
 
Slides920
Slides920Slides920
Slides920
 
Spectroscopic fiber optic catheter tania - aha 2001
Spectroscopic fiber optic catheter  tania - aha 2001Spectroscopic fiber optic catheter  tania - aha 2001
Spectroscopic fiber optic catheter tania - aha 2001
 
Slager1
Slager1Slager1
Slager1
 
Seferovic
SeferovicSeferovic
Seferovic
 
Pasterkamp2
Pasterkamp2Pasterkamp2
Pasterkamp2
 
Rumberg2
Rumberg2Rumberg2
Rumberg2
 
Phil graham new
Phil graham newPhil graham new
Phil graham new
 
Ppt for adelson sketch
Ppt for adelson  sketchPpt for adelson  sketch
Ppt for adelson sketch
 
Out of hospital sudden cardiac death (scd) declining or escalating
Out of hospital sudden cardiac death (scd) declining or escalatingOut of hospital sudden cardiac death (scd) declining or escalating
Out of hospital sudden cardiac death (scd) declining or escalating
 

More from Society for Heart Attack Prevention and Eradication

More from Society for Heart Attack Prevention and Eradication (20)

AHA SHAPE Symposium 2017 Dr. Naghavi Presentation
AHA SHAPE Symposium 2017 Dr. Naghavi PresentationAHA SHAPE Symposium 2017 Dr. Naghavi Presentation
AHA SHAPE Symposium 2017 Dr. Naghavi Presentation
 
AHA SHAPE Symposium 2017 Dr. Kloner Presentation
AHA SHAPE Symposium 2017 Dr. Kloner PresentationAHA SHAPE Symposium 2017 Dr. Kloner Presentation
AHA SHAPE Symposium 2017 Dr. Kloner Presentation
 
AHA SHAPE Symposium 2017 Dr. Greenland Presentation
AHA SHAPE Symposium 2017 Dr. Greenland PresentationAHA SHAPE Symposium 2017 Dr. Greenland Presentation
AHA SHAPE Symposium 2017 Dr. Greenland Presentation
 
AHA SHAPE Symposium 2017 Dr. Yen Presentation
AHA SHAPE Symposium 2017 Dr. Yen PresentationAHA SHAPE Symposium 2017 Dr. Yen Presentation
AHA SHAPE Symposium 2017 Dr. Yen Presentation
 
AHA SHAPE Symposium 2017 Dr. Slomka Presentation
AHA SHAPE Symposium 2017 Dr. Slomka PresentationAHA SHAPE Symposium 2017 Dr. Slomka Presentation
AHA SHAPE Symposium 2017 Dr. Slomka Presentation
 
Vu lplaque1 pasterkamp
Vu lplaque1 pasterkampVu lplaque1 pasterkamp
Vu lplaque1 pasterkamp
 
Vulnerable plaque vulnerable patient
Vulnerable plaque vulnerable patientVulnerable plaque vulnerable patient
Vulnerable plaque vulnerable patient
 
Vulnerable plaque overview
Vulnerable plaque overviewVulnerable plaque overview
Vulnerable plaque overview
 
Vulnerable patient talk in poland
Vulnerable patient talk in polandVulnerable patient talk in poland
Vulnerable patient talk in poland
 
Vulnerable patient slides without movies
Vulnerable patient slides without moviesVulnerable patient slides without movies
Vulnerable patient slides without movies
 
Vulnerable patient mar 04
Vulnerable patient mar 04Vulnerable patient mar 04
Vulnerable patient mar 04
 
Vulnerable (thrombogenic blood
Vulnerable (thrombogenic bloodVulnerable (thrombogenic blood
Vulnerable (thrombogenic blood
 
Vuln shape aha 2005
Vuln shape aha 2005Vuln shape aha 2005
Vuln shape aha 2005
 
Vuln plaque poster burke
Vuln plaque poster burkeVuln plaque poster burke
Vuln plaque poster burke
 
Vp watch editorial_slide 25short-
Vp watch editorial_slide 25short-Vp watch editorial_slide 25short-
Vp watch editorial_slide 25short-
 
Vp watch editorial_slide25
Vp watch editorial_slide25Vp watch editorial_slide25
Vp watch editorial_slide25
 
Vp watch editorial_slide25short-
Vp watch editorial_slide25short-Vp watch editorial_slide25short-
Vp watch editorial_slide25short-
 
Vp watch2002
Vp watch2002Vp watch2002
Vp watch2002
 
Vp symposium31602
Vp symposium31602Vp symposium31602
Vp symposium31602
 
Vpschoenhagen
VpschoenhagenVpschoenhagen
Vpschoenhagen
 

Recently uploaded

Adenomyosis or Fibroid- making right diagnosis
Adenomyosis or Fibroid- making right diagnosisAdenomyosis or Fibroid- making right diagnosis
Adenomyosis or Fibroid- making right diagnosisSujoy Dasgupta
 
Different drug regularity bodies in different countries.
Different drug regularity bodies in different countries.Different drug regularity bodies in different countries.
Different drug regularity bodies in different countries.kishan singh tomar
 
BENIGN BREAST DISEASE
BENIGN BREAST DISEASE BENIGN BREAST DISEASE
BENIGN BREAST DISEASE Mamatha Lakka
 
Forensic Nursing powerpoint presentation
Forensic Nursing powerpoint presentationForensic Nursing powerpoint presentation
Forensic Nursing powerpoint presentationKavitha Krishnan
 
A presentation on Thermal gravimetry analysis (TGA)
A presentation on Thermal gravimetry analysis (TGA)A presentation on Thermal gravimetry analysis (TGA)
A presentation on Thermal gravimetry analysis (TGA)1922Jaygohel
 
pA2 value, Schild plot and pD2 values- applications in pharmacology
pA2 value, Schild plot and pD2 values- applications in pharmacologypA2 value, Schild plot and pD2 values- applications in pharmacology
pA2 value, Schild plot and pD2 values- applications in pharmacologyDeepakDaniel9
 
Male Infertility, Antioxidants and Beyond
Male Infertility, Antioxidants and BeyondMale Infertility, Antioxidants and Beyond
Male Infertility, Antioxidants and BeyondSujoy Dasgupta
 
Mental health Team. Dr Senthil Thirusangu
Mental health Team. Dr Senthil ThirusanguMental health Team. Dr Senthil Thirusangu
Mental health Team. Dr Senthil Thirusangu Medical University
 
Bulimia nervosa ( Eating Disorders) Mental Health Nursing.
Bulimia nervosa ( Eating Disorders) Mental Health Nursing.Bulimia nervosa ( Eating Disorders) Mental Health Nursing.
Bulimia nervosa ( Eating Disorders) Mental Health Nursing.aarjukhadka22
 
Trustworthiness of AI based predictions Aachen 2024
Trustworthiness of AI based predictions Aachen 2024Trustworthiness of AI based predictions Aachen 2024
Trustworthiness of AI based predictions Aachen 2024EwoutSteyerberg1
 
Arthroscopic Surgery in Indore : A Minimally Invasive Guide to Joint Health
Arthroscopic Surgery in Indore : A Minimally Invasive Guide to Joint HealthArthroscopic Surgery in Indore : A Minimally Invasive Guide to Joint Health
Arthroscopic Surgery in Indore : A Minimally Invasive Guide to Joint HealthGokuldas Hospital
 
AI in Action: Elevating Patient Insights
AI in Action: Elevating Patient InsightsAI in Action: Elevating Patient Insights
AI in Action: Elevating Patient InsightsEmily Kunka, MS, CCRP
 
Basic structure of hair and hair growth cycle.pptx
Basic structure of hair and hair growth cycle.pptxBasic structure of hair and hair growth cycle.pptx
Basic structure of hair and hair growth cycle.pptxkomalt2001
 
Generative AI in Health Care a scoping review and a persoanl experience.
Generative AI in Health Care a scoping review and a persoanl experience.Generative AI in Health Care a scoping review and a persoanl experience.
Generative AI in Health Care a scoping review and a persoanl experience.Vaikunthan Rajaratnam
 
PAIN/CLASSIFICATION AND MANAGEMENT OF PAIN.pdf
PAIN/CLASSIFICATION AND MANAGEMENT OF PAIN.pdfPAIN/CLASSIFICATION AND MANAGEMENT OF PAIN.pdf
PAIN/CLASSIFICATION AND MANAGEMENT OF PAIN.pdfDolisha Warbi
 
SGK NGẠT NƯỚC ĐHYHN RẤT LÀ HAY NHA .pdf
SGK NGẠT NƯỚC ĐHYHN RẤT LÀ HAY NHA    .pdfSGK NGẠT NƯỚC ĐHYHN RẤT LÀ HAY NHA    .pdf
SGK NGẠT NƯỚC ĐHYHN RẤT LÀ HAY NHA .pdfHongBiThi1
 
AORTIC DISSECTION and management of aortic dissection
AORTIC DISSECTION and management of aortic dissectionAORTIC DISSECTION and management of aortic dissection
AORTIC DISSECTION and management of aortic dissectiondrhanifmohdali
 
Neurological history taking (2024) .
Neurological  history  taking  (2024)  .Neurological  history  taking  (2024)  .
Neurological history taking (2024) .Mohamed Rizk Khodair
 
blood bank management system project report
blood bank management system project reportblood bank management system project report
blood bank management system project reportNARMADAPETROLEUMGAS
 

Recently uploaded (20)

Adenomyosis or Fibroid- making right diagnosis
Adenomyosis or Fibroid- making right diagnosisAdenomyosis or Fibroid- making right diagnosis
Adenomyosis or Fibroid- making right diagnosis
 
Different drug regularity bodies in different countries.
Different drug regularity bodies in different countries.Different drug regularity bodies in different countries.
Different drug regularity bodies in different countries.
 
BENIGN BREAST DISEASE
BENIGN BREAST DISEASE BENIGN BREAST DISEASE
BENIGN BREAST DISEASE
 
Forensic Nursing powerpoint presentation
Forensic Nursing powerpoint presentationForensic Nursing powerpoint presentation
Forensic Nursing powerpoint presentation
 
A presentation on Thermal gravimetry analysis (TGA)
A presentation on Thermal gravimetry analysis (TGA)A presentation on Thermal gravimetry analysis (TGA)
A presentation on Thermal gravimetry analysis (TGA)
 
pA2 value, Schild plot and pD2 values- applications in pharmacology
pA2 value, Schild plot and pD2 values- applications in pharmacologypA2 value, Schild plot and pD2 values- applications in pharmacology
pA2 value, Schild plot and pD2 values- applications in pharmacology
 
Male Infertility, Antioxidants and Beyond
Male Infertility, Antioxidants and BeyondMale Infertility, Antioxidants and Beyond
Male Infertility, Antioxidants and Beyond
 
Mental health Team. Dr Senthil Thirusangu
Mental health Team. Dr Senthil ThirusanguMental health Team. Dr Senthil Thirusangu
Mental health Team. Dr Senthil Thirusangu
 
Bulimia nervosa ( Eating Disorders) Mental Health Nursing.
Bulimia nervosa ( Eating Disorders) Mental Health Nursing.Bulimia nervosa ( Eating Disorders) Mental Health Nursing.
Bulimia nervosa ( Eating Disorders) Mental Health Nursing.
 
Trustworthiness of AI based predictions Aachen 2024
Trustworthiness of AI based predictions Aachen 2024Trustworthiness of AI based predictions Aachen 2024
Trustworthiness of AI based predictions Aachen 2024
 
Immune labs basics part 1 acute phase reactants ESR, CRP Ahmed Yehia Ismaeel,...
Immune labs basics part 1 acute phase reactants ESR, CRP Ahmed Yehia Ismaeel,...Immune labs basics part 1 acute phase reactants ESR, CRP Ahmed Yehia Ismaeel,...
Immune labs basics part 1 acute phase reactants ESR, CRP Ahmed Yehia Ismaeel,...
 
Arthroscopic Surgery in Indore : A Minimally Invasive Guide to Joint Health
Arthroscopic Surgery in Indore : A Minimally Invasive Guide to Joint HealthArthroscopic Surgery in Indore : A Minimally Invasive Guide to Joint Health
Arthroscopic Surgery in Indore : A Minimally Invasive Guide to Joint Health
 
AI in Action: Elevating Patient Insights
AI in Action: Elevating Patient InsightsAI in Action: Elevating Patient Insights
AI in Action: Elevating Patient Insights
 
Basic structure of hair and hair growth cycle.pptx
Basic structure of hair and hair growth cycle.pptxBasic structure of hair and hair growth cycle.pptx
Basic structure of hair and hair growth cycle.pptx
 
Generative AI in Health Care a scoping review and a persoanl experience.
Generative AI in Health Care a scoping review and a persoanl experience.Generative AI in Health Care a scoping review and a persoanl experience.
Generative AI in Health Care a scoping review and a persoanl experience.
 
PAIN/CLASSIFICATION AND MANAGEMENT OF PAIN.pdf
PAIN/CLASSIFICATION AND MANAGEMENT OF PAIN.pdfPAIN/CLASSIFICATION AND MANAGEMENT OF PAIN.pdf
PAIN/CLASSIFICATION AND MANAGEMENT OF PAIN.pdf
 
SGK NGẠT NƯỚC ĐHYHN RẤT LÀ HAY NHA .pdf
SGK NGẠT NƯỚC ĐHYHN RẤT LÀ HAY NHA    .pdfSGK NGẠT NƯỚC ĐHYHN RẤT LÀ HAY NHA    .pdf
SGK NGẠT NƯỚC ĐHYHN RẤT LÀ HAY NHA .pdf
 
AORTIC DISSECTION and management of aortic dissection
AORTIC DISSECTION and management of aortic dissectionAORTIC DISSECTION and management of aortic dissection
AORTIC DISSECTION and management of aortic dissection
 
Neurological history taking (2024) .
Neurological  history  taking  (2024)  .Neurological  history  taking  (2024)  .
Neurological history taking (2024) .
 
blood bank management system project report
blood bank management system project reportblood bank management system project report
blood bank management system project report
 

Slides 29 38

  • 1. Secretion and Regulation of ApoB48 by Primary Hamster Intestinal EnterocytesIntestinal Enterocytes B C LabeledApoB48(%control) LabeledApoB48(%control) 0 20 40 60 80 100 120 Total Cells Media Control MG132 P < 0.05 0 20 40 60 80 100 120 Total Cells Media Control Oleate P = 0.01 Cells Media 0 45 90 45 90 A Chase Time (min)
  • 2. Cells Media Fructose-Fed Chow-Fed Chase Time (Min) 0 45 90 45 90 D Chase Time (Min) Chase Time (Min) 100 100 0 10 20 30 40 50 60 70 80 90 0 20 40 60 80 Total apoB 48 LabeledApoB48(%of0Time) LabeledApoB48(%of0Time) p= 0.003 p= 0.001 Secreted apoB 48 0 10 20 30 40 50 60 70 80 90 100 0 20 40 60 80 100 Chow-Fed Fructose-Fed E F Ex vivo evidence for oversecretion of intestinal apoB48 & Enhanced intracellular apoB48 stability in fructose- fed hamster enterocytes
  • 3. In Vivo Production of TG & Intestinal ApoB48 in the Fasting State Time (min) 55 60 65 70 75 80 85 Sf>400TGconcentration (mmol/l) 0 1 2 3 4 Sf >400 after Triton WR1339 Time (min) 55 60 65 70 75 80 85 Sf>400ApoB48concentration (µg/ml) 140 160 180 200 220 240 260 280 Time (min) 55 60 65 70 75 80 85 Sf100-400TGconcentration (mmol/l) 0 1 2 3 Sf 100-400 after Triton WR1339 Time (min) 55 60 65 70 75 80 85 Sf100-400ApoB48concentration (µg/ml) 90 100 110 120 130 140 150 160 170 Triglyceridesecretion 0.0 0.2 0.4 0.6 0 1 2 3 ApoB48secretion 0 4 8 12 16 Triglyceridesecretion 0.0 0.1 0.2 0.3 ApoB48secretion 0 2 4 6p = 0.002 p = 0.01 p = 0.14 p = 0.59 A B DC
  • 4. In Vivo Production of TG & Intestinal ApoB48 in the Postprandial State Time (min) 55 60 65 70 75 80 85 Triglyceridelevel(mmol/l) 0.0 0.1 0.2 0.3 0.4 0.5 0.6 Time (min) 55 60 65 70 75 80 85 ApoB48level(µg/ml) 80 90 100 110 120 130 140 150 Time (min) 55 60 65 70 75 80 85 Triglyceridelevel(mmol/l) 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 Time (min) 55 60 65 70 75 80 85 ApoB48level(µg/ml) 50 60 70 80 90 100 Triglyceridesecretion(µmol/min) 0.00 0.01 0.02 0.03 0.04 0.05 0.06 0.07 Col 48: 0.07 Col 48: 0.06 Triglyceridesecretion(µmol/min) 0.00 0.02 0.04 0.06 0.08 0.10 Col 50: 0.08 Col 50: 0.09 0 1 2 3 ApoB48secretion(µg/min) 0 1 2 3 4 5 6 7 8 Col 52: 2.65 Col 52: 7.46 ApoB48secretion(µg/min) 0 1 2 3 4 5 6 7 8 Col 54: 3.85 Col 54: 7.26 Sf 100-400 after Triton WR1339 Sf >400 after Triton WR1339 A B C D p = 0.3 p = 0.003 p = 0.8 p = 0.007
  • 5. 0 20 40 60 80 100 120 140 160 Fructose-Fed MTPProteinMass (%ofControl) Chow-Fed Fructose-Fed 0 20 40 60 80 100 120 0 0.5 1 1.5 2 2.5 3 3.5 MTP inhibitor (µM) ApoB48Secretion(%ofcontrol) Fructose-fed Chow-fed ∗ ∗ ∗ ∗ Chow-Fed p=0.006D E LabeledCholesterylEster (%ofControl) p= 0.002 0 50 100 150 200 250 Cellular p=0.001 Media B LabeledCholesterol (%ofControl) Chow-Fed Fructose-Fed 0 100 200 300 400 500 600 700 800 Cellular p=0.0018 p=0.0013A Media LabeledTriglyceride (%ofControl) Cellular 0 20 40 60 80 100 120 140 160 180 p=0.04 p=0.003 Media C Ex Vivo Evidence for Intestinal Overproduction of Lipoprotein Lipids and Increase MTP mass/activity
  • 6. Fructose-Fed Chow-fed 0 10 20 30 40 50 60 70 80 Large CM Small CM VLDL LDL HDL p<0.05 p= 0.06 p<0.03 %ofTotalLabeledApoB48 A 0 20 40 60 80 100 120 140 CM apoB48 Total-apoB48 LabeledApoB48 (%ofFructose-fed) p<0.0007 p<0.01C 0 10 20 30 40 50 60 70 80 Particles< 1.006 Particles > 1.006 %ofTotalLabeledAPoB48 p<0.024 p<0.026 B 0 40 20 60 80 100 120 CM apoB48 Total apoB48 LabeledApoB48 (%ofFructose-fed) P=0.008 P=0.0001 DFasting Postprandial Density/Size Distribution of Intestinal Lipoproteins Evidence for Increased Number & Size
  • 7. Increased De Novo Lipogenesis in FF Enterocytes Evidence that ApoB48 Secretion is Linked to the Rate of De Novo Lipogenesis 0 10 20 30 40 50 60 70 80 90 100 110 0 2 4 6 8 10 12 14 16 Cholesterol Fatty Acid Triglyceride LabeledLipid(%ascontrol) Cerulenin µg/ml 0 50 100 150 200 250 300 350 Chow-fed Fructose-fed LabeledFattyAcid(%ascontrol) 0 10 20 30 40 50 60 70 80 90 100 110 0 2 4 6 8 10 12 14 16 Cerulenin µg/ml LabeledSecretedApoB-48(%ascontrol) A C p= 0.002 Sensitivity of ApoB48 Secretion to Cerulenin Fatty Acid Synthesis Sensitivity of TG & FA Secretion to Cerulenin
  • 8. 20 60 80 100 0 40 120 Chow-fed Fructose-fed (2 days) 0 20 40 60 80 100 120 Control Fructose (3mM ) 0 200 400 600 800 1000 enterocytes hepatocytes P < 0.01 LabeledApoB-48(%ofcontrol) LabeledApoB-48(%ofcontrol) Labeledcholesterol 0 50 100 150 200 250 300 350 400 450 enterocytes hepatocytes LabeledTriglyceride P < 0.0001 Acute Fructose Feeding or Exposure Does NOT Affect Intestinal ApoB48 Secretion [14 C] Fructose Incorporation into TG & Cholesterol Two-day Fructose Feeding In Vitro Incubation of Enterocytes with Fructose
  • 9. Mechanisms of Intestinal Lipoprotein Overproduction in Insulin Resistant/ Hyperinsulinemic States Apical Surface Basolateral Surface FA monoglyceride FABP-FA FABP TG TG TG ApoB48 PL CE De Novo (FA) Insulin (??) TGdietary SOS Grb-2 IRS PI3-K p110 SHP-2 NCK PTKPTK β β α α IR PKB (Akt) SREBP1c FAS & ACC Glucose + FA MTP ERER GolgiGolgi Intestinal Enterocyte TG ApoB48 Lipoprotein Particles p85Proteasome Degradation
  • 10. Acknowledgements Laboratory Group: Changiz Taghibiglou Mehran Haidari Steven Van Iderstine Wei Qui Taryne Chong Farhana Mahboob Biao Chen Leyla Mangaloglu Louisa Pontrelli Fariborz Rashid Rita Kohen Debbie Rudy Collaborators: Gary Lewis- Toronto Andre Carpentier- Sherbrooke Sven Olof Olofsson - Sweden Janet Sparks - Rochester, NY Raphael Cheung – Windsor Michel Tremblay – Montreal Denny Trinh - Toronto Funding: Heart & Stroke Foundation of Ontario Canadian Institutes of Health Research NSERC Hospital for Sick Children Merck-Frosst pfizer GlaxoSmithKline BBDC, University of Toronto