Dual-Function Intravascular Catheter for Atherosclerosis Diagnostics

We herein present a novel intravascular catheter, with dual-functions of electrical impedance spectroscopy (EIS) and flow fraction reserve (FFR), validated in live pig animal for atherosclerosis/plaques diagnostics. FFR has been the standard tool in determining plaque vulnerability yet could produce false negative results when stenosis is relatively small. Meanwhile, EIS has been demonstrated to specifically distinguish the lipid-rich pool, the signifying feature of rupture-prone plaques. The synergetic performance of these two functionalities can significantly enhance state-of-art diagnostics accuracy for atherosclerosis

Dual-Function Intravascular Catheter for Atherosclerosis Diagnostics

We herein present a novel intravascular catheter, with dual-functions of electrical impedance spectroscopy (EIS) and flow fraction reserve (FFR), validated in live pig animal for atherosclerosis/plaques diagnostics. FFR has been the standard tool in determining plaque vulnerability yet could produce false negative results when stenosis is relatively small. Meanwhile, EIS has been demonstrated to specifically distinguish the lipid-rich pool, the signifying feature of rupture-prone plaques. The synergetic performance of these two functionalities can significantly enhance state-of-art diagnostics accuracy for atherosclerosis

Double-Ballooned Local Drug Delivery Catheter with Blood Bypassing Function

We present a double-ballooned catheter that enables both local drug delivery and blood bypassing at the same time. Such catheters are targeted for high-dose local drug treatment of cardiovascular diseases, such as atherosclerosis and restenosis, allowing for extended use without causing downstream ischemia. The device is composed of two flexible balloons that can isolate the lesion under inflation. Local drug delivery can be achieved using the inner catheters while a blood bypassing catheter allows for continuous blood flow. The functionalities of the catheter are validated in both benchtop and live pig experiments

Double-Ballooned Local Drug Delivery Catheter with Blood Bypassing Function

We present a double-ballooned catheter that enables both local drug delivery and blood bypassing at the same time. Such catheters are targeted for high-dose local drug treatment of cardiovascular diseases, such as atherosclerosis and restenosis, allowing for extended use without causing downstream ischemia. The device is composed of two flexible balloons that can isolate the lesion under inflation. Local drug delivery can be achieved using the inner catheters while a blood bypassing catheter allows for continuous blood flow. The functionalities of the catheter are validated in both benchtop and live pig experiments

Haploinsufficiency of mechanistic target of rapamycin ameliorates cardiomyopathy in adult zebrafish

The adult zebrafish is an emerging vertebrate model for studying human cardiomyopathies; however, whether the simple zebrafish heart can model different subtypes of cardiomyopathies, such as dilated cardiomyopathy (DCM), remains elusive. Here, we generated and characterized an inherited DCM model in adult zebrafish and used this model to search for therapeutic strategies. We employed transcription activator-like effector nuclease (TALEN) genome editing technology to generate frame-shift mutants for the zebrafish ortholog of human BCL2-associated athanogene 3 (BAG3), an established DCM-causative gene. As in mammals, the zebrafish bag3 homozygous mutant (bag3e2/e2 ) exhibited aberrant proteostasis, as indicated by impaired autophagy flux and elevated ubiquitinated protein aggregation. Through comprehensive phenotyping analysis of the mutant, we identified phenotypic traits that resembled DCM phenotypes in mammals, including cardiac chamber enlargement, reduced ejection fraction characterized by increased end-systolic volume/body weight (ESV/BW), and reduced contractile myofibril activation kinetics. Nonbiased transcriptome analysis identified the hyperactivation of the mechanistic target of rapamycin (mTOR) signaling in bag3e2/e2 mutant hearts. Further genetic studies showed that mtorxu015/+ , an mTOR haploinsufficiency mutant, repaired abnormal proteostasis, improved cardiac function and rescued the survival of the bag3e2/e2 mutant. This study established the bag3e2/e2 mutant as a DCM model in adult zebrafish and suggested mtor as a candidate therapeutic target gene for BAG3 cardiomyopathy.This work was supported in part by the Scientist Development Grant from the American Heart Association (14SDG18160021) to Y.D., the Ted and Loretta Rogers Cardiovascular Career Development Award Honoring Hugh C. Smith (from the Mayo Clinic) to Y.D., the National Institutes of Health (HL81753, HL107304, HL111437 and GM63904) to X.X., and the Mayo Foundation for Medical Education and Research to X.X.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]