scholarly journals Cardiac gene therapy with type 2 phosphodiesterase (PDE2) in experimental heart failure: Complementary or alternative to β–blockers?

2022 ◽  
Vol 14 (1) ◽  
pp. 100
Author(s):  
J. Larue ◽  
R. Kamel ◽  
D. Mika ◽  
S. Gomez ◽  
J. Leroy ◽  
...  
Keyword(s):  
Heart Failure ◽  
Gene Therapy ◽  
Experimental Heart Failure ◽  
Cardiac Gene ◽  
Β Blockers

scholarly journals Cardiac gene therapy of heart failure with phosphodiesterase PDE4B in mice

2019 ◽  
Vol 11 (2) ◽  
pp. 224-225
Author(s):  
A. Bourcier ◽  
C. Coquard ◽  
J. Margaria ◽  
S. Gomez ◽  
A. Varin ◽  
...  
Keyword(s):  
Heart Failure ◽  
Gene Therapy ◽  
Cardiac Gene

scholarly journals Molecular cardiomyoplasty: Potential cardiac gene therapy for chronic heart failure

1995 ◽  
Vol 109 (5) ◽  
pp. 918-924 ◽  
Author(s):  
Stanley K.C. Tam ◽  
Wei Gu ◽  
Bernardo Nadal-Ginard
Keyword(s):  
Heart Failure ◽  
Gene Therapy ◽  
Chronic Heart Failure ◽  
Cardiac Gene

scholarly journals Perspective of the β-blockers for the patients with diabetes and heart failure 

2020 ◽  
Vol 8 (4) ◽  
pp. 97-99
Author(s):  
Hiroshi BANDO
Keyword(s):  
Heart Failure ◽  
Adverse Outcomes ◽  
Control Group ◽  
Sodium Glucose Cotransporter ◽  
Strict Glycemic Control ◽  
Cardiovascular Assessment ◽  
Patients With Diabetes ◽  
Outcome Trial ◽  
Β Blockers

Patients with diabetes and heart failure have been increasing due to Japanese Cardiac Registry of Heart Failure in Cardiology (JCARE-CARD) study. β-blockers showed significantly suppressed cardiovascular events in the strict glycemic control group. Sodium-glucose Cotransporter-2 Inhibitors (SGLT2i) seem to be beneficial for diabetes and heart failure. Clinical efficacy of β-blockers would be suggested from three studies including Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients-Removing Excess Glucose (EMPA-REG OUTCOME) trial, Canagliflozin cardioVascular Assessment Study (CANVAS) and Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) study. Further discussion will be expected with research in detail.

scholarly journals Gene therapy targeting cardiac phosphoinositide 3-kinase (p110α) attenuates cardiac remodeling in type 2 diabetes

2020 ◽  
Vol 318 (4) ◽  
pp. H840-H852 ◽  
Author(s):  
Darnel Prakoso ◽  
Miles J. De Blasio ◽  
Mitchel Tate ◽  
Helen Kiriazis ◽  
Daniel G. Donner ◽  
...  
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Gene Therapy ◽  
Cause Of Death ◽  
Diabetic Cardiomyopathy ◽  
Cardiac Remodeling ◽  
Systolic Dysfunction ◽  
Phosphoinositide 3 Kinase ◽  
Fractional Shortening

Diabetic cardiomyopathy is a distinct form of heart disease that represents a major cause of death and disability in diabetic patients, particularly, the more prevalent type 2 diabetes patient population. In the current study, we investigated whether administration of recombinant adeno-associated viral vectors carrying a constitutively active phosphoinositide 3-kinase (PI3K)(p110α) construct (rAAV6-caPI3K) at a clinically relevant time point attenuates diabetic cardiomyopathy in a preclinical type 2 diabetes (T2D) model. T2D was induced by a combination of a high-fat diet (42% energy intake from lipid) and low-dose streptozotocin (three consecutive intraperitoneal injections of 55 mg/kg body wt), and confirmed by increased body weight, mild hyperglycemia, and impaired glucose tolerance (all P < 0.05 vs. nondiabetic mice). After 18 wk of untreated diabetes, impaired left ventricular (LV) systolic dysfunction was evident, as confirmed by reduced fractional shortening and velocity of circumferential fiber shortening (Vcfc, all P < 0.01 vs. baseline measurement). A single tail vein injection of rAAV6-caPI3K gene therapy (2×1011vector genomes) was then administered. Mice were followed for an additional 8 wk before end point. A single injection of cardiac targeted rAAV6-caPI3K attenuated diabetes-induced cardiac remodeling by limiting cardiac fibrosis (reduced interstitial and perivascular collagen deposition, P < 0.01 vs. T2D mice) and cardiomyocyte hypertrophy (reduced cardiomyocyte size and Nppa gene expression, P < 0.001 and P < 0.05 vs. T2D mice, respectively). The diabetes-induced LV systolic dysfunction was reversed with rAAV6-caPI3K, as demonstrated by improved fractional shortening and velocity of circumferential fiber shortening (all P < 0.05 vs pre-AAV measurement). This cardioprotection occurred in combination with reduced LV reactive oxygen species ( P < 0.05 vs. T2D mice) and an associated decrease in markers of endoplasmic reticulum stress (reduced Grp94 and Chop, all P < 0.05 vs. T2D mice). Together, our findings demonstrate that a cardiac-selective increase in PI3K(p110α), via rAAV6-caPI3K, attenuates T2D-induced diabetic cardiomyopathy, providing proof of concept for potential translation to the clinic. NEW & NOTEWORTHY Diabetes remains a major cause of death and disability worldwide (and its resultant heart failure burden), despite current care. The lack of existing management of heart failure in the context of the poorer prognosis of concomitant diabetes represents an unmet clinical need. In the present study, we now demonstrate that delayed intervention with PI3K gene therapy (rAAV6-caPI3K), administered as a single dose in mice with preexisting type 2 diabetes, attenuates several characteristics of diabetic cardiomyopathy, including diabetes-induced impairments in cardiac remodeling, oxidative stress, and function. Our discovery here contributes to the previous body of work, suggesting the cardioprotective effects of PI3K(p110α) could be a novel therapeutic approach to reduce the progression to heart failure and death in diabetes-affected patients.

scholarly journals Cholesterol-Lowering Gene Therapy Prevents Heart Failure with Preserved Ejection Fraction in Obese Type 2 Diabetic Mice

2019 ◽  
Vol 20 (9) ◽  
pp. 2222 ◽  
Author(s):  
Joseph Pierre Aboumsallem ◽  
Ilayaraja Muthuramu ◽  
Mudit Mishra ◽  
Bart De Geest
Keyword(s):  
Heart Failure ◽  
Gene Therapy ◽  
Gene Transfer ◽  
Ejection Fraction ◽  
Plasma Cholesterol ◽  
Preserved Ejection Fraction ◽  
Ldlr Gene ◽  
Lung Weight ◽  
Cholesterol Lowering

Hypercholesterolemia may be causally related to heart failure with preserved ejection fraction (HFpEF). We aimed to establish a HFpEF model associated with hypercholesterolemia and type 2 diabetes mellitus by feeding a high-sucrose/high-fat (HSHF) diet to C57BL/6J low-density lipoprotein receptor (LDLr)−/− mice. Secondly, we evaluated whether cholesterol-lowering adeno-associated viral serotype 8 (AAV8)-mediated LDLr gene transfer prevents HFpEF. AAV8-LDLr gene transfer strongly (p < 0.001) decreased plasma cholesterol in standard chow (SC) mice (66.8 ± 2.5 mg/dl versus 213 ± 12 mg/dl) and in HSHF mice (84.6 ± 4.4 mg/dl versus 464 ± 25 mg/dl). The HSHF diet induced cardiac hypertrophy and pathological remodeling, which were potently counteracted by AAV8-LDLr gene transfer. Wet lung weight was 19.0% (p < 0.001) higher in AAV8-null HSHF mice than in AAV8-null SC mice, whereas lung weight was normal in AAV8-LDLr HSHF mice. Pressure–volume loop analysis was consistent with HFpEF in AAV8-null HSHF mice and showed a completely normal cardiac function in AAV8-LDLr HSHF mice. Treadmill exercise testing demonstrated reduced exercise capacity in AAV8-null HSHF mice but a normal capacity in AAV8-LDLr HSHF mice. Reduced oxidative stress and decreased levels of tumor necrosis factor-α may mediate the beneficial effects of cholesterol lowering. In conclusion, AAV8-LDLr gene therapy prevents HFpEF.

scholarly journals Recent advances in cardiac gene therapy strategies targeting advanced heart failure

2017 ◽  
Vol 3 (4) ◽  
pp. 163-169 ◽  
Author(s):  
C. Chen ◽  
T. Seeger ◽  
V. Termglinchan ◽  
I. Karakikes
Keyword(s):  
Heart Failure ◽  
Gene Therapy ◽  
Advanced Heart Failure ◽  
Recent Advances ◽  
Cardiac Gene ◽  
Therapy Strategies
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