Ingenuity pathway analysis of the human cardiac cell Atlas identifies differences between right and left ventricular cardiomyocytes

Prisco, Sasha Z.; Kazmirczak, Felipe; Thenappan, Thenappan; Prins, Kurt W.

doi:10.1002/pul2.12011

Cited by 3 publications

(2 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Those with RV dysfunction were less likely to recover LV systolic function during follow-up (46% vs. 68%). Mean PASP was higher in the RV dysfunction group [median (IQR): 37 mmHg (24-43)] vs. the group with preserved RV function [median (IQR): 26 (23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)]. Women with RV dysfunction had greater baseline and follow-up LV end-diastolic and end-systolic diameter.…”

Section: Resultsmentioning

confidence: 99%

“…Studies have also found differences between the LV and RV at the molecular level, which may in part explain predisposition to RV dysfunction in some patients. The ingenuity pathway analysis (a bioinformatics application integrating omics with genomic and clinical data) from the Human Heart Cell Atlas identified some molecular differences between the RV and LV including higher levels of sarcomeric proteins titin, beta oestradiol, and the ryanodine receptor in the RV 35 . Future studies are needed to further understand these genotype–phenotype correlations.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Clinical predictors of right ventricular dysfunction and association with adverse outcomes in peripartum cardiomyopathy

Imran,

Ataklte,

Khalid

et al. 2023

ESC Heart Failure

View full text Add to dashboard Cite

AimsWe sought to identify factors associated with right ventricular (RV) dysfunction and elevated pulmonary artery systolic pressure (PASP) and association with adverse outcomes in peripartum cardiomyopathy (PPCM).Methods and resultsWe conducted a multi‐centre cohort study to identify subjects with PPCM with the following criteria: left ventricular ejection fraction (LVEF) < 40%, development of heart failure within the last month of pregnancy or 5 months of delivery, and no other identifiable cause of heart failure with reduced ejection fraction. Outcomes included a composite of (i) major adverse events (need for extracorporeal membrane oxygenation, ventricular assist device, orthotopic heart transplantation, or death) or (ii) recurrent heart failure hospitalization. RV function was obtained from echocardiogram reports. In total, 229 women (1993–2017) met criteria for PPCM. Mean age was 32.4 ± 6.8 years, 28% were of African descent, 50 (22%) had RV dysfunction, and 38 (17%) had PASP ≥ 30 mmHg. After a median follow‐up of 3.4 years (interquartile range 1.0–8.8), 58 (25%) experienced the composite outcome of adverse events. African descent, family history of cardiomyopathy, LVEF, and PASP were significant predictors of RV dysfunction. Using Cox proportional hazards models, we found that women with RV dysfunction were three times more likely to experience the adverse composite outcome: hazard ratio 3.21 (95% confidence interval: 1.11–9.28), P = 0.03, in a multivariable model adjusting for age, race, body mass index, preeclampsia, hypertension, diabetes, kidney disease, and LVEF. Women with PASP ≥ 30 mmHg had a lower probability of survival free from adverse events (log‐rank P = 0.04).ConclusionsAfrican descent and family history of cardiomyopathy were significant predictors of RV dysfunction. RV dysfunction and elevated PASP were significantly associated with a composite of major adverse cardiac events. This at‐risk group may prompt closer monitoring or early referral for advanced therapies.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Clinical predictors of right ventricular dysfunction and association with adverse outcomes in peripartum cardiomyopathy

Imran,

Ataklte,

Khalid

et al. 2023

ESC Heart Failure

View full text Add to dashboard Cite

show abstract

Ingenuity pathway analysis of the human cardiac cell Atlas identifies differences between right and left ventricular cardiomyocytes

et al. 2022

Self Cite

View full text Add to dashboard Cite

show abstract

Molecular and physiological mechanisms of aging are distinct in the cardiac right and left ventricles

McNair,

Yusifov,

Thornburg

et al. 2024

Aging Cell

View full text Add to dashboard Cite

Aging is the primary risk factor for heart disease, the leading global cause of death. Right ventricular (RV) function predicts survival in several age‐related clinical contexts, yet no therapies directly improve RV function, in large part due to a poor mechanistic understanding of RV aging and how it is distinct from the widely studied left ventricle (LV). To address this gap, we comprehensively quantified RV functional and morphological remodeling with age. We further aimed to identify molecular mechanisms of RV aging thus we performed RNAseq on RV and LV from male and female young (4 months) and aged (19–21 months) C57BL6 mice. Contrary to the concentric hypertrophic remodeling and diastolic dysfunction that occurs in the LV, the aging RV underwent eccentric remodeling with significant dilation and impaired systolic function. Transcriptomic data were also consistent with ventricle‐specific aging, with few genes (13%) similarly shared between ventricles with aging. KEGG analysis identified shared aging genes in inflammatory and immune cell pathways that were confirmed by flow cytometry that demonstrated higher percent of GR1+ myeloid cells in both ventricles. Unique RV aging genes enriched in the biosynthesis of saturated fatty acids, PPAR signaling, and butanoate metabolism, and we identified putative novel RV‐specific aging genes. Together, we suggest that the RV and LV are unique cardiac chambers that undergo distinct remodeling with age. These robust differences may explain why therapies designed from LV‐based studies fail to improve RV function and suggest that future efforts emphasizing ventricular differences may elucidate new therapies for healthy cardiac aging.

show abstract

Ingenuity pathway analysis of the human cardiac cell Atlas identifies differences between right and left ventricular cardiomyocytes

Cited by 3 publications

References 15 publications

Clinical predictors of right ventricular dysfunction and association with adverse outcomes in peripartum cardiomyopathy

Clinical predictors of right ventricular dysfunction and association with adverse outcomes in peripartum cardiomyopathy

Ingenuity pathway analysis of the human cardiac cell Atlas identifies differences between right and left ventricular cardiomyocytes

Molecular and physiological mechanisms of aging are distinct in the cardiac right and left ventricles

Contact Info

Product

Resources

About