Final Presentation

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MCP-1 and MIP-3α Expression in LCR/HCR Rats Dr. Anuska Andjelkovic Lab By: Zarion Marshall

Transcript of Final Presentation

Page 1: Final Presentation

MCP-1 and MIP-3α Expression in LCR/HCR RatsDr. Anuska Andjelkovic Lab By: Zarion Marshall

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Low Capacity Runners (LCR) and High Capacity Runners (HCR) Rats

• LCR rats are highly susceptible to cardiovascular diseases like atherosclerosis

• LCR rats are insulin resistant

• Natural screening model (no gene manipulation)

• Grouped by simple measure of treadmill running distance

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My Rats

• Generation 23• About 46-48 weeks old (~10-11 months)• All female for lower variability of body weight

LCR HCR0.00

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LCR more sensitive to harmful effects of high fat diet

• Overall high body weight

• Higher fat percentage

• Higher food intake

• Higher serum leptin levels (mostly adipose)

Credit: Colleen M. Novak, Carlos Escande, Paul R. Burghardt, Minzhi Zhang, Maria Teresa Barbosa, Eduardo N. Chini, Steven L. Britton, Lauren G. Koch, Huda Akil, James A. Levine in “Spontaneous activity, economy of activity, and resistance to diet-induced obesity in rats bred for high intrinsic aerobic capacity”

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Activity and Energy Expenditure

• LCR less active (not dependent on body weight) and expend less energy

Credit: Colleen M. Novak, Carlos Escande, Paul R. Burghardt, Minzhi Zhang, Maria Teresa Barbosa, Eduardo N. Chini, Steven L. Britton, Lauren G. Koch, Huda Akil, James A. Levine in “Spontaneous activity, economy of activity, and resistance to diet-induced obesity in rats bred for high intrinsic aerobic capacity”

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Energy Expenditure and Respiratory Exchange Rate (RER)• LCR lower

energy expenditure even in rest

• Also higher RER which suggests ineffecient use of lipids

Credit: Colleen M. Novak, Carlos Escande, Paul R. Burghardt, Minzhi Zhang, Maria Teresa Barbosa, Eduardo N. Chini, Steven L. Britton, Lauren G. Koch, Huda Akil, James A. Levine in “Spontaneous activity, economy of activity, and resistance to diet-induced obesity in rats bred for high intrinsic aerobic capacity”

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Hypothesis• LCR rats are most susceptible to proinflammatory

factors which leaves the blood brain barrier (BBB) at risk for microvascular changes like stroke

• Chemokines on basolateral (brain) side of barrier attract leukocytes from the apical (blood) side

Goal• Investigate the chemokines monocyte

chemotactic protein (MCP-1) and macrophage inflammatory protein (MIP-3α) and their role in the BBB’s integrity

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Blood Brain Barrier

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How It Works (Supposedly)

• Proinflammatory proteins cause barrier to lose integrity between endothelial cells

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Protein Array (Vessels)

Leptin 349.67 63.58 0.181829

LIX 308.76 984.77 3.189435

L-Selectin 192.28 603.06 3.136364

MCP-1 311.31 1,782.95 5.727249

MIP-3α 39.78 779.87 19.60458

MMP-8 144.55 383.52 2.6532

PDGF-AA 4,323.15 3,028.13 0.700445

Prolactin R 4,737.59 5,581.02 1.178029

RAGE 3,582.80 6,503.18 1.815111

Thymus Chemokine-1 4,596.71 7,274.25 1.582491

TIMP-1 178.61 982.7 5.501932

HCR

LCR

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LCR

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Cytokine Expression

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MCP-1(Tissue ELISA)

• 0.03 ng/ml HCR• 1.12 ng/ml LCR

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MIP-3α (Tissue ELISA)

• 0.14 pg/ml HCR• 2.72 pg/ml LCR

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Staining

• Red=chemokine • Green=astrocyte• MIP-3α seems to be

mostly in astrocytes • You can see from the

staining as well not as much of either in HCR

• We think MCP-1 is more in microglia…

LCR HCR

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Conclusion• The higher inflammatory risk of LCR rats explains

at least in part their phenotype which resembles classic metabolic syndrome conditions

• MCP-1 and MIP-3α contribute are indeed factors that differentiate the two LCR and HCR phenotypes and suggests that a role in microvascular changes

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Much Thanks to…• Svetlana and Nikola • And of course Dr. Andjelkovic