We summarize the significant recent progress that has been made in treating heart failure in preclinically relevant animal models with AAV gene therapy and the recent results of clinical trials with cardiac AAV gene therapy for the treatment of heart failure.
AAV gene delivery elevated the intracellular expression of the AR185 protein in a rat model of ischemic HF, and this treatment normalized the systolic and diastolic dysfunction of the failing myocardium <i>in vivo</i> by reversing myocardial Ca<sup>2+</sup> handling.
Many molecular targets selected to treat heart failure using AAV gene therapy have been chosen because of their potential to regulate and restore cardiac contractility.
The ATP-binding cassette transporter ABCG2 protects against pressure overload-induced cardiac hypertrophy and heart failure by promoting angiogenesis and antioxidant response.
The aim of the present study was to evaluate the effects of ABCB1 gene polymorphism and P-gp inhibitor co-administration on steady-state digoxin serum concentration in congestive heart failure patients.
This study aimed to evaluate the influence of CYP3A5 and ABCB1 genotypes on tolvaptan pharmacokinetics and their relationships with plasma markers of CYP3A activity and laboratory test values in heart failure patients.
Effect of ABCB1 (MDR1) 3435C >T and 2677G >A,T polymorphisms and P-glycoprotein inhibitors on salivary digoxin secretion in congestive heart failure patients.
In conclusion, an association between ABCB1 haplotype and plasma fasting LDL cholesterol concentration was found in patients with advanced heart failure.
This study included a randomly selected subcohort (n=502), cardiovascular disease (CVD) cases (n=245), and heart failure cases (n=220) from the Health, Aging, and Body Composition (Health ABC) Study.
In patients without HF at baseline (89.9%), we derived the 5-year risk for incident HF using the 9-variable Health ABCHF Risk score [classified as low-to-average (<10%), high (10-20%), and very high (≥ 20%)].
In this study, we included Health ABC study (Health, Aging, and Body Composition) participants without prevalent HF who had arterial stiffness measured as carotid-femoral pulse wave velocity (cf-PWV) at baseline (n=2290).
ABCB7 was found to interact with mitochondrial complexes IV and V. We conclude that in chronic pressure overload, ABCB7 deficiency results in iron overload and mitochondrial dysfunction, contributing to heart failure.
Multivariate analysis revealed that the odds of CHF was higher in females [Odds Ratio (OR) = 2·9, P < 0·01], individuals with pre-HCT chest radiation (OR = 4·7, P = 0·05), hypertension (OR = 2·9, P = 0·01), and with variants of genes coding for the NAD(P)H-oxidase subunit RAC2 (rs13058338, 7508T→A; OR = 2·8, P < 0·01), HFE (rs1799945, 63C→G; OR = 2·5, P = 0·05) or the doxorubicin efflux transporter ABCC2 (rs8187710, 1515G→A; OR = 4·3, P < 0·01).
We also analyzed the mRNA expression of the K(ATP) targets K(ir)6.1, K(ir)6.2, SUR1, and SUR2 in the left atria and ventricles of NF (n=8) and CHF (n=4) hearts.
Scanning of genomic DNA from individuals with heart failure and rhythm disturbances due to idiopathic dilated cardiomyopathy identified two mutations in ABCC9, which encodes the regulatory SUR2A subunit of the cardiac K(ATP) channel.
We also analyzed the mRNA expression of the K(ATP) targets K(ir)6.1, K(ir)6.2, SUR1, and SUR2 in the left atria and ventricles of NF (n=8) and CHF (n=4) hearts.
The ATP-binding cassette transporter ABCG2 protects against pressure overload-induced cardiac hypertrophy and heart failure by promoting angiogenesis and antioxidant response.
ABO blood type distribution in the HF population was not significantly different to that reported in the general national population (A 40%, B 20%, AB 8%, and O 33%).