©2018 by Kass Lab.

RECENT PUBLICATIONS

LEVERAGING SIGNALING PATHWAYS TO TREAT HEART FAILURE WITH REDUCED EJECTION FRACTION.

May 2019 Circ Res

Advances in the treatment of heart failure with reduced ejection fraction due to systolic dysfunction are engaging an ever-expanding compendium of molecular signaling targets. This review explores therapies that have proven successful, those that have not, those that are moving into the clinic but whose utility remains to be confirmed, and those that remain in the experimental realm.

IN VIVO SELECTIVE INHIBITION OF TRPC6 BY ANTAGONIST BI 749327 AMELIORATES FIBROSIS AND DYSFUNCTION IN CARDIAC AND RENAL DISEASE

April 2019 PNAS

New TRPC6 inhibitor tested in mouse models of heart and kidney disease

PKG1-MODIFIED TSC2 REGULATES MTORC1 ACTIVITY TO COUNTER ADVERSE CARDIAC STRESS

January 2019 Nature

How Viagra Puts A Brake on A Master Growth Regulator to Treat Heart Disease
#NewBreak4HeartBreak

CHRONIC ATRIAL AND VENTRICULAR PACING IN THE MOUSE

February 2019 Circ Heart Fail

The new method to chronically pace conscious mice yields stable atrial and ventricular capture and a means to dissect basic mechanisms of electromechanical physiology and therapy.

MARKED DISPARITY OF MICRORNA MODULATION BY CGMP-SELECTIVE PDE5 VERSUS PDE9 INHIBITORS IN HEART DISEASE

August 2018 JCI Insight

Seemingly similar therapeutic interventions can be barcoded by profound differences in miR signatures, and reversing disease-associated miR changes is not required for therapy success.

ACUTE ENHANCEMENT OF CARDIAC FUNCTION BY PHOSPHODIESTERASE TYPE 1 INHIBITION

October 2018 Circulation

Blocking PDE1 improves short-term heart function

TRANSIENT RECEPTOR POTENTIAL CHANNEL 6 REGULATES ABNORMAL CARDIAC S-NITROSYLATION IN DUCHENNE MUSCULAR DYSTROPHY

December 2017 PNAS

These findings reveal a role for Trpc6-mediated hypernitrosylation in Duchenne muscular dystrophy and support accumulating evidence that implicates nitrosative stress in cardiac and muscle disease.

NEONATAL TRANSPLANTATION CONFERS MATURATION OF PSC-DERIVED CARDIOMYOCYTES CONDUCIVE TO MODELING CARDIOMYOPATHY

January 2017 Cell Rep

Pluripotent stem cells (PSCs) offer unprecedented opportunities for disease modeling and personalized medicine. This study lays a foundation for understanding human CM maturation and pathogenesis and can be instrumental in PSC-based modeling of adult heart diseases.

TETRAHYDROBIOPTERIN PROTECTS AGAINST HYPERTROPHIC HEART DISEASE INDEPENDENT OF MYOCARDIAL NITRIC OXIDE SYNTHASE COUPLING

March 2016 J Am Heart Assoc

Nitric oxide synthase uncoupling occurs under conditions of oxidative stress modifying the enzyme's function so it generates superoxide rather than nitric oxide. BH4 protection against adverse remodeling in hypertrophic cardiac disease is not driven by its prevention of myocardial nitric oxide synthase uncoupling, as presumed previously. Instead, benefits from exogenous BH4 are mediated by a protective effect coupled to suppression of inflammatory pathways and myocardial macrophage infiltration.

PACEMAKER-INDUCED TRANSIENT ASYNCHRONY SUPPRESSES HEART FAILURE PROGRESSION.

Dec 2015 Sci Transl Med

Uncoordinated contraction from electromechanical delay worsens heart failure pathophysiology and prognosis, but restoring coordination with biventricular pacing, known as cardiac resynchronization therapy (CRT), improves both. Results suggest that PITA could bring the benefits of CRT to the many heart failure patients with synchronous contraction who are not CRT candidates.

DUAL LABELING BIOTIN SWITCH ASSAY TO REDUCE BIAS DERIVED FROM DIFFERENT CYSTEINE SUBPOPULATIONS: A METHOD TO MAXIMIZE S-NITROSYLATION DETECTION

January 25, 2025

S-nitrosylation (SNO), an oxidative post-translational modification of cysteine residues, responds to changes in the cardiac redox-environment. Using a protocol comprising 2 tags for dual-labeling maximizes overall detection of SNO by reducing the previously unrecognized labeling bias derived from different cysteine subpopulations.

PREVENTION OF PKG1Α OXIDATION AUGMENTS CARDIOPROTECTION IN THE STRESSED HEART

June 2015 JCI

The cGMP-dependent protein kinase-1α (PKG1α) transduces NO and natriuretic peptide signaling; therefore, PKG1α activation can benefit the failing heart. These results demonstrate that myocardial PKG1α oxidation prevents a beneficial response to pathological stress, may explain variable responses to PKG1α pathway stimulation in heart disease, and indicate that maintaining PKG1α in its reduced form may optimize its intrinsic cardioprotective properties.

PHOSPHODIESTERASE 9A CONTROLS NITRIC-OXIDE-INDEPENDENT CGMP AND HYPERTROPHIC HEART DISEASE

March 2015 Nature

Cyclic guanosine monophosphate (cGMP) is a second messenger molecule that transduces nitric-oxide- and natriuretic-peptide-coupled signalling, stimulating phosphorylation changes by protein kinase G. PDE9A can regulate cGMP signalling independent of the nitric oxide pathway, and its role in stress-induced heart disease suggests potential as a therapeutic target.

SOLUBLE GUANYLATE CYCLASE IS REQUIRED FOR SYSTEMIC VASODILATION BUT NOT POSITIVE INOTROPY INDUCED BY NITROXYL IN THE MOUSE

February 2015 Hypertension

Nitroxyl (HNO), the reduced and protonated form of nitric oxide (NO·), confers unique physiological effects including vasorelaxation and enhanced cardiac contractility. sGC and cGMP-dependent signaling are necessary and sufficient for HNO-induced vasodilation in vivo but are not required for positive inotropic action. Redox modulation of protein kinase G-1α is not a mechanism for HNO-mediated vasodilation.

 

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