Medicine and Health Sciences Commons^™

Gadolinium Free Cardiovascular Magnetic Resonance With 2-Point Cine Balanced Steady State Free Precession, Tori A. Stromp, Steve W. Leung, Kristin N Andres, Linyuan Jing, Brandon K. Fornwalt, Richard Charnigo, Vincent L. Sorrell, Moriel H. Vandsburger

Saha Cardiovascular Research Center Faculty Publications

BACKGROUND: Cardiovascular magnetic resonance (CMR) of ventricular structure and function is widely performed using cine balanced steady state free precession (bSSFP) MRI. The bSSFP signal of myocardium is weighted by magnetization transfer (MT) and T1/T2-relaxation times. In edematous and fibrotic tissues, increased T2 and reduced MT lead to increased signal intensity on images acquired with high excitation flip angles. We hypothesized that acquisition of two differentially MT-weighted bSSFP images (termed 2-point bSSFP) can identify tissue that would enhance with gadolinium similar to standard of care late gadolinium enhancement (LGE).

METHODS: Cine bSSFP images (flip angles of 5° and …

Effects Of Adipocyte Aryl Hydrocarbon Receptor Deficiency On Pcb-Induced Disruption Of Glucose Homeostasis In Lean And Obese Mice, Nicki A. Baker, Robin Shoemaker, Victoria English, Nika Larian, Manjula Sunkara, Andrew J. Morris, Mary Walker, Frederique Yiannikouris, Lisa A. Cassis

Saha Cardiovascular Research Center Faculty Publications

BACKGROUND: Coplanar polychlorinated biphenyls (PCBs) promote adipocyte inflammation and impair glucose homeostasis in lean mice. The diabetes-promoting effects of lipophilic PCBs have been observed only during weight loss in obese mice. The molecular mechanisms linking PCB exposures to impaired glucose metabolism are unclear.

OBJECTIVES: In this study we tested the hypothesis that coplanar PCBs act at adipocyte aryl hydrocarbon receptors (AhRs) to promote adipose inflammation and impair glucose homeostasis in lean mice and in obese mice during weight loss.

METHODS AND RESULTS: PCB-77 administration impaired glucose and insulin tolerance in LF (low fat diet)-fed control (AhR^fl/fl) mice …

Lipin1 Regulates Skeletal Muscle Differentiation Through Extracellular Signal-Regulated Kinase (Erk) Activation And Cyclin D Complex-Regulated Cell Cycle Withdrawal, Weihua Jiang, Jing Zhu, Xun Zhuang, Xiping Zhang, Tao Luo, Karyn Esser, Hongmei Ren

Saha Cardiovascular Research Center Faculty Publications

Lipin1, an intracellular protein, plays critical roles in controlling lipid synthesis and energy metabolism through its enzymatic activity and nuclear transcriptional functions. Several mouse models of skeletal muscle wasting are associated with lipin1 mutation or altered expression. Recent human studies have suggested that children with homozygous null mutations in the LPIN1 gene suffer from rhabdomyolysis. However, the underlying pathophysiologic mechanism is still poorly understood. In the present study we examined whether lipin1 contributes to regulating muscle regeneration. We characterized the time course of skeletal muscle regeneration in lipin1-deficient fld mice after injury. We found that fld mice exhibited smaller regenerated …

Left Ventricular Mechanical Dysfunction In Diet-Induced Obese Mice Is Exacerbated During Inotropic Stress: A Cine Dense Cardiovascular Magnetic Resonance Study, Christopher M. Haggerty, Andrea C. Mattingly, Sage P. Kramer, Cassi M. Binkley, Linyuan Jing, Jonathan D. Suever, David K. Powell, Richard J. Charnigo, Frederick H. Epstein, Brandon K. Fornwalt

Saha Cardiovascular Research Center Faculty Publications

BACKGROUND: Obesity is a risk factor for cardiovascular disease. There is evidence of impaired left ventricular (LV) function associated with obesity, which may relate to cardiovascular mortality, but some studies have reported no dysfunction. Ventricular function data are generally acquired under resting conditions, which could mask subtle differences and potentially contribute to these contradictory findings. Furthermore, abnormal ventricular mechanics (strains, strain rates, and torsion) may manifest prior to global changes in cardiac function (i.e., ejection fraction) and may therefore represent more sensitive markers of cardiovascular disease. This study evaluated LV mechanics under both resting and stress conditions with the hypothesis …

Exogenous 17-Β Estradiol Administration Blunts Progression Of Established Angiotensin Ii-Induced Abdominal Aortic Aneurysms In Female Ovariectomized Mice, Sean E. Thatcher, Xuan Zhang, Shannon Woody, Yu Wang, Yasir Alsiraj, Richard Charnigo, Alan Daugherty, Lisa A. Cassis

Saha Cardiovascular Research Center Faculty Publications

BACKGROUND: Abdominal aortic aneurysms (AAAs) occur predominately in males. However, AAAs in females have rapid growth rates and rupture at smaller sizes. Mechanisms contributing to AAA progression in females are undefined. We defined effects of ovariectomy, with and without 17-β estradiol (E2), on progression of established angiotensin II (AngII)-induced AAAs in female mice.

METHODS: We used neonatal testosterone exposures at 1 day of age to promote susceptibility to AngII-induced AAAs in adult female Ldlr^-/- mice. Females were infused with AngII for 28 days to induce AAAs, and then stratified into groups that were sham, ovariectomized (Ovx, vehicle), or Ovx …

Telemetric Blood Pressure Assessment In Angiotensin Ii-Infused Apoe-/- Mice: 28 Day Natural History And Comparison To Tail-Cuff Measurements, Christopher M. Haggerty, Andrea C. Mattingly, Ming C. Gong, Wen Su, Alan Daugherty, Brandon K. Fornwalt

Saha Cardiovascular Research Center Faculty Publications

Abdominal aortic aneurysm (AAA) is a disease of the aortic wall, which can progress to catastrophic rupture. Assessment of mechanical characteristics of AAA, such as aortic distensibility, may provide important insights to help identify at-risk patients and understand disease progression. While the majority of studies on this topic have focused on retrospective patient data, recent studies have used mouse models of AAA to prospectively evaluate the evolution of aortic mechanics. Quantification of aortic distensibility requires accurate measurement of arterial blood pressure, particularly pulse pressure, which is challenging to perform accurately in murine models. We hypothesized that volume/pressure tail-cuff measurements of …

Validation Of In Vivo 2d Displacements From Spiral Cine Dense At 3t, Gregory J. Wehner, Jonathan D. Suever, Christopher M. Haggerty, Linyuan Jing, David K. Powell, Sean M. Hamlet, Jonathan D. Grabau, Walter Dimitri Mojsejenko, Xiaodong Zhong, Frederick H. Epstein, Brandon K. Fornwalt

Saha Cardiovascular Research Center Faculty Publications

BACKGROUND: Displacement Encoding with Stimulated Echoes (DENSE) encodes displacement into the phase of the magnetic resonance signal. Due to the stimulated echo, the signal is inherently low and fades through the cardiac cycle. To compensate, a spiral acquisition has been used at 1.5T. This spiral sequence has not been validated at 3T, where the increased signal would be valuable, but field inhomogeneities may result in measurement errors. We hypothesized that spiral cine DENSE is valid at 3T and tested this hypothesis by measuring displacement errors at both 1.5T and 3T in vivo.

METHODS: Two-dimensional spiral cine DENSE and tagged …

The Tmao-Generating Enzyme Flavin Monooxygenase 3 Is A Central Regulator Of Cholesterol Balance, Manya Warrier, Diana M. Shih, Amy C. Burrows, Daniel Ferguson, Anthony D. Gromovsky, Amanda L. Brown, Stephanie Marshall, Allison Mcdaniel, Rebecca C. Schugar, Zeneng Wang, Jessica Sacks, Xin Rong, Thomas De Aguiar Vallim, Jeff Chou, Pavlina T. Ivanova, David S. Myers, H. Alex Brown, Richard G. Lee, Rosanne M. Crooke, Mark J. Graham, Xiuli Liu, Paolo Parini, Peter Tontonoz, Aldon J. Lusis, Stanley L. Hazen, Ryan E. Temel, J. Mark Brown

Saha Cardiovascular Research Center Faculty Publications

Circulating levels of the gut microbe-derived metabolite trimethylamine-N-oxide (TMAO) have recently been linked to cardiovascular disease (CVD) risk. Here, we performed transcriptional profiling in mouse models of altered reverse cholesterol transport (RCT) and serendipitously identified the TMAO-generating enzyme flavin monooxygenase 3 (FMO3) as a powerful modifier of cholesterol metabolism and RCT. Knockdown of FMO3 in cholesterol-fed mice alters biliary lipid secretion, blunts intestinal cholesterol absorption, and limits the production of hepatic oxysterols and cholesteryl esters. Furthermore, FMO3 knockdown stimulates basal and liver X receptor (LXR)-stimulated macrophage RCT, thereby improving cholesterol balance. Conversely, FMO3 knockdown exacerbates hepatic endoplasmic reticulum (ER) stress …