Molecular Approaches in HFpEF: MicroRNAs and iPSC-Derived Cardiomyocytes

Abstract

Heart failure with preserved left ventricular ejection fraction (HFpEF) has emerged as one of the largest unmet needs in cardiovascular medicine. HFpEF is increasing in prevalence and causes significant morbidity, mortality, and health care resource utilization. Patients have multiple co-morbidities which contribute to the disease complexity. To date, no effective treatment for HFpEF has been identified. The paucity of cardiac biopsies from this patient population and the absence of well-accepted animal models limit our understanding of the underlying molecular mechanisms of HFpEF. In this review, we discuss combining state-of-the-art technologies of microRNA profiling and human induced plu-ripotent cell-derived cardiomyocytes (iPSC-CMs) in order to uncover novel molecular pathways that may contribute to the development of HFpEF. Here, we focus the advantages and limitations of microRNA profiling and iPSC-CMs as a disease model system to discover molecular mechanisms in HFpEF.

An integrative translational approach to study heart failure with preserved ejection fraction: a position paper from the Working Group on Myocardial Function of the European Society of Cardiology

“…Dysfunctional interactions between cardiac cell‐types have been proposed, but while various intercellular communication disturbances have been well documented in related experimental models and cell culture experiments, few were documented in HFpEF . Further developments in co‐culture methods and conditioned medium exposure applied to HFpEF samples may provide important clues, as well as research on engineered tissues and human induced pluripotent cell‐derived cardiomyocytes . The high‐order cross‐talk between the heart and lung, skeletal muscle, adipose tissue (AT), and kidney in HF is increasingly acknowledged, but its particular features in HFpEF remain poorly investigated.…”

“…99 Further developments in co-culture methods and conditioned medium exposure applied to HFpEF samples may provide important clues, as well as research on engineered tissues and human induced pluripotent cell-derived cardiomyocytes. 100 The high-order cross-talk between the heart and lung, skeletal muscle, adipose tissue (AT), and kidney in HF is increasingly acknowledged, 99 but its particular features in HFpEF remain poorly investigated. The lungs are the first organ that are directly affected in HFpEF, pre-capillary and post-capillary components, as well as pulmonary vascular ED have been well established.…”

Myokines and Heart Failure: Challenging Role in Adverse Cardiac Remodeling, Myopathy, and Clinical Outcomes

“…Finally, both cardiac hypertrophy and interstitial fibrosis contribute to diastolic abnormalities and the development of HFpEF [ 12 ]. In contrast, HFrEF is directly related to sufficient loss of the cardiac myocytes due to necrosis resulting of ischemia, inflammation, and apoptosis that are associated with adverse cardiac remodeling, systemic neurohormonal activation, peripheral vascular effects, skeletal muscle dysfunction, and metabolic abnormalities [ 13 , 14 ]. However, the impaired physical activity due to muscle weakness, skeletal myopathy, muscle atrophy, and finally cachexia is the attributive factor for HF progression and it is closely associated with increased CV mortality, HF hospitalization, and decrease in the quality of life [ 15 ].…”

Precision Medicine for Heart Failure with Preserved Ejection Fraction: An Overview

“…These papers cover a variety of topics relevant to precision medicine, including text mining and natural language processing to identify HFpEF patients [11]; tensor factorization, a promising machine learning technique that can be applied to the field of HFpEF [10]; molecular approaches to precision medicine in HFpEF (induced pluripotent stem cell-derived cardiomyocytes and microRNAs) [9]; genome-wide characterization of molecular profiles of HFpEF [7]; deep phenotyping of arterial hemodynamics in HFpEF [5,6]; phenomapping of hypertension to identify the myocardial substrate for HFpEF [8]; and finally innovative clinical trial designs that can be used to advance precision medicine in HFpEF [12]. …”