Doxorubicin induces wide-spread transcriptional changes in the myocardium of hearts distinguishing between mice with preserved and impaired cardiac function

Abstract Background Cannabis use in pregnancy leads to fetal growth restriction (FGR), but the long-term effects on cardiac function in the offspring are unknown, despite the fact that fetal growth deficits are associated with an increased risk of developing postnatal cardiovascular disease. We hypothesize that maternal exposure to Δ9-tetrahydrocannabinol (Δ9-THC) during pregnancy will impair fetal development, leading to cardiac dysfunction in the offspring. Methods Pregnant Wistar rats were randomly selected and administered 3 mg/kg of Δ9-THC or saline as a vehicle daily via intraperitoneal injection from gestational days 6 to 22, followed by echocardiogram analysis of cardiac function on offspring at postnatal days 1 and 21. Heart tissue was harvested from the offspring at 3 weeks for molecular analysis of cardiac remodelling. Results Exposure to Δ9-THC during pregnancy led to FGR with a significant decrease in heart-to-body weight ratios at birth. By 3 weeks, pups exhibited catch-up growth associated with significantly greater left ventricle anterior wall thickness with a decrease in cardiac output. Moreover, these Δ9-THC-exposed offsprings exhibited increased expression of collagen I and III, decreased matrix metallopeptidase-2 expression, and increased inactivation of glycogen synthase kinase-3β, all associated with cardiac remodelling. Conclusions Collectively, these data suggest that Δ9-THC-exposed FGR offspring undergo postnatal catch-up growth concomitant with cardiac remodelling and impaired cardiac function early in life. Impact To date, the long-term effects of perinatal Δ9-THC (the main psychoactive component) exposure on the cardiac function in the offspring remain unknown. We demonstrated, for the first time, that exposure to Δ9-THC alone during rat pregnancy results in significantly smaller hearts relative to body weight. These Δ9-THC-exposed offsprings exhibited postnatal catch-up growth concomitant with cardiac remodelling and impaired cardiac function. Given the increased popularity of cannabis use in pregnancy along with rising Δ9-THC concentrations, this study, for the first time, identifies the risk of perinatal Δ9-THC exposure on early postnatal cardiovascular health.

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Abnormal Cardiac Development in the Absence of Heart Glycogen

Molecular and Cellular Biology ◽

10.1128/mcb.24.16.7179-7187.2004 ◽

2004 ◽

Vol 24 (16) ◽

pp. 7179-7187 ◽

Cited By ~ 68

Author(s):

Bartholomew A. Pederson ◽

Hanying Chen ◽

Jill M. Schroeder ◽

Weinian Shou ◽

Anna A. DePaoli-Roach ◽

...

Keyword(s):

Cardiac Function ◽

Cardiac Muscle ◽

Heart Development ◽

Congenital Heart ◽

Cardiac Development ◽

Glycogen Synthase ◽

Heart Defects ◽

Mendelian Inheritance ◽

And Function ◽

Impaired Cardiac Function

ABSTRACT Glycogen serves as a repository of glucose in many mammalian tissues. Mice lacking this glucose reserve in muscle, heart, and several other tissues were generated by disruption of the GYS1 gene, which encodes an isoform of glycogen synthase. Crossing mice heterozygous for the GYS1 disruption resulted in a significant underrepresentation of GYS1-null mice in the offspring. Timed matings established that Mendelian inheritance was followed for up to 18.5 days postcoitum (dpc) and that ∼90% of GYS1-null animals died soon after birth due to impaired cardiac function. Defects in cardiac development began between 11.5 and 14.5 dpc. At 18.5 dpc, the hearts were significantly smaller, with reduced ventricular chamber size and enlarged atria. Consistent with impaired cardiac function, edema, pooling of blood, and hemorrhagic liver were seen. Glycogen synthase and glycogen were undetectable in cardiac muscle and skeletal muscle from the surviving null mice, and the hearts showed normal morphology and function. Congenital heart disease is one of the most common birth defects in humans, at up to 1 in 50 live births. The results provide the first direct evidence that the ability to synthesize glycogen in cardiac muscle is critical for normal heart development and hence that its impairment could be a significant contributor to congenital heart defects.

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Local delivery of a senolytic drug in ischemia and reperfusion-injured heart attenuates cardiac remodeling and restores impaired cardiac function

Acta Biomaterialia ◽

10.1016/j.actbio.2021.08.028 ◽

2021 ◽

Author(s):

Ju-Ro Lee ◽

Bong-Woo Park ◽

Jae-Hyun Park ◽

Songhyun Lim ◽

Sung Pil Kwon ◽

...

Keyword(s):

Cardiac Function ◽

Cardiac Remodeling ◽

Local Delivery ◽

Ischemia And Reperfusion ◽

Impaired Cardiac Function

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Impaired Cardiac Function in Metabolic Syndrome

Canadian Journal of Cardiology ◽

10.1016/j.cjca.2014.01.012 ◽

2014 ◽

Vol 30 (3) ◽

pp. 270-271 ◽

Cited By ~ 1

Author(s):

David Fitchett ◽

Kim A. Connelly

Keyword(s):

Metabolic Syndrome ◽

Cardiac Function ◽

Impaired Cardiac Function

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Abstract 13764: Chronic Electronic Cigarette Vapor Exposure Leads to Impaired Cardiac Function in Experimental Rat Myocardial Ischemia/reperfusion Model

Circulation ◽

10.1161/circ.142.suppl_3.13764 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Wangde Dai ◽

Jianru Shi ◽

Juan Carreno ◽

Lifu Zhao ◽

Michael T Kleinman ◽

...

Keyword(s):

Coronary Artery ◽

Cardiac Function ◽

Wall Thickness ◽

Ischemia Reperfusion ◽

Coronary Artery Occlusion ◽

Artery Occlusion ◽

Risk Zone ◽

Arterial Resistance ◽

No Reflow ◽

Impaired Cardiac Function

Background: We investigated the effects of long-term electronic cigarettes with nicotine (eC) vaping on cardiac function and structure in rats subjected to myocardial infarction (MI). Methods: After 8 weeks of exposure to either pure air (n=20) or eC (n=20), rats were anesthetized, and were subjected to 30 minutes of coronary artery occlusion followed by 3 hours of reperfusion. Cardiac function was assessed by echocardiogram and pressure measurements of the aorta and left ventricle (LV). Cardiac output (CO) was measured using a thermodilution catheter. At 3 hours of reperfusion, ischemic risk zone, no-reflow and infarct areas were determined. Results: Prior to coronary artery occlusion, chronic eC exposure was associated with a lower CO (45 ± 2 ml/min ) compared to air (55 ± 4 ml/min; p<0.05)) and a decrease in +dP/dt (5226 ± 294 mmHg/s versus 6062 ± 271 mmHg/s; p=0.05). After 30 minutes of coronary occlusion and 2.5 hours of reperfusion, CO and LV + dp/dt fell in both groups, but remained significantly lower in eC compared to the pure air group (Table). LV systolic and diastolic dimensions were significantly smaller in the E-Cig group compared to the air group. Systolic and diastolic anterior LV wall thickness were significantly thicker in the eC group after reperfusion. The ischemic risk size was comparable between the 2 groups. MI size was 48.8 ± 4.8% of the ischemic risk zone in the air group and 45.4 ± 4.4 % in the eC group (p=0.603). The area of no reflow was 26.7 ± 4.0% of the ischemic risk zone in the air group and 21.1 ± 3.5% in the E-C group (p=0.298). Chronic eC exposure did not change heart rate and blood pressure, but the significantly increased the systemic arterial resistance. Conclusions: Chronic exposure to eC significantly impaired cardiac function in rats prior to and during ischemia/reperfusion, increased arterial resistance, but did not increase infarct size or no-reflow zone. Increased LV wall thickness of the risk zone suggested that eC may have increased edema.

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