AC6 and Cardiac Function.
| Model | Findings | Ref | |
|---|---|---|---|
| TG Mice | AC6 : Cardiac-Directed Expression | Basal HR, cAMP, LV dP/dt unaffected; increased recruitable LV dP/dt, no adverse effects at 24 months | 59 |
| AC6 × Gq (CHF) | AC6 expressed in Gq-associated cardiomyopathy: increased LV function & survival, decreased LVH | 50, 54 | |
| AC6 TG × Gq TG (CHF) | AC6 expressed in Gq-associated cardiomyopathy: increased LV SERCA2a activity and PLN phosphorylation | 56 | |
| AC6 : Regulated and Cardiac-Directed | Increased LV function in normal adult mice upon activation of LV AC6 expression | 69 | |
| AC6 : Regulated and Cardiac-Directed (CHF) | Activation of LV AC6 expression increased function of failing heart | 57 | |
| AC6 & Acute MI | Mortality >50% reduced in mice with increased cardiac AC6 content - similar to propranolol treatment | 51 | |
| AC6 × Gq (CHF) | AC6 expressed in Gq-associated cardiomyopathy: corrects prolonged action potential duration | 52 | |
| AC6 : Cardiac-Directed Expression | AC6 expression is associated with facilitation of AV conduction in normal mice | 53 | |
| AC6 : Cardiac-Directed Expression | AC6 expression does not affect mean HR, HR variability, vagal responsiveness, or activity levels (telemetry) | 97 | |
| AC6 Deletion | Adverse effects on LV Ca2+ signaling; reduced LV function | 93 | |
| Ad. AC6 Gene Transfer | Neonatal Rat Cardiac Myocytes | AC6 amount determines cardiac myocyte response to βAR stimulation | 58 |
| Neonatal Rat Cardiac Myocytes | AC6 increases ATF3 expression with consequent reduced PLN expression (cAMP independent) | 70 | |
| Neonatal Rat Cardiac Myocytes | AC6 activates Akt with consequent PLN phosphorylation (cAMP independent) | 71 | |
| Neonatal Rat Cardiac Myocytes | AC6 associated with dynamic regulation of Akt via PHLPP:AC6 interaction (cAMP-independent) | 72 | |
| Neonatal Rat Cardiac Myocytes | Ad. AC6 Ad. vs β1AR: differences in intracellular distribution of transgene contribute to differences in outcome | 81 | |
| Adult Rat Cardiac Myocytes | AC6 & AC6 mutant (catalytically inactive) have similar benefits: mechanism is cAMP-independent | 83 | |
| CHF, Mouse | AC6 gene transfer (indirect intracoronary) in Gq-associated cardiomyopathy: increased function of failing LV | 98 | |
| Normal Mouse | AC6 gene transfer (indirect intracoronary) increases LV function in response to βAR stimulation | 99 | |
| Normal Pig | AC6 gene transfer (intracoronary + histamine) increases recruitable LV dP/dt | 64 | |
| CHF, Pig | AC6 gene transfer (intracoronary + nitroprusside) increases function of failing LV | 55,68 | |
| Normal Pig | IND App: AC6 gene transfer (intracoronary + nitroprusside) not toxic; LV AC6 expression persists 10 weeks | * | |
| CHF, Human | Intracoronary Ad. hAC6 in patients with severe CHF (Phase 1 /Phase 2 randomized double-blind clinical trial) | * |
*
see ClinicalTrials.gov #NCT00787059, enrollment for this clinical trial was initiated in May 2010