## 6 LncRNAs and Cardiovascular Disease
### Roles of LncRNAs in Cardiac Hypertrophy and Heart Failure  
Cardiac hypertrophy is the thickening of the myocardium and the subsequent heart failure, which is caused by a maladaptive response of the heart, is a common heart disease in the United States. Cardiac hypertrophy is associated with pressure or volume overload in the heart during various heart diseases such as hypertension and valve stenosis. In the initial phase of cardiac hypertrophy, the heart muscle begins to thicken, thus decreasing the chamber size and cardiac output. Cardiomyocytes then attempt to compensate for the decreased cardiac output by increasing their sizes. The imbalance between nutrient supply and demand in cardiomyocytes eventually leads to heart failure [3]. In 2013, over five million individuals had heart failure in the United States, prompting an urgent need for therapeutic and preventative solutions [62].  
Clusters of lncRNAs have been associated with cardiac hypertrophy [9,42,44]. In pathological hypertrophy, [PERSON] _et al._, identified a cluster of lncRNAs transcribed from _Myh7_ loci and demonstrated a new mechanism for heart failure (lncRNA-chromatin mechanism) [41]. _Myh7_ undergoes antisense transcription to produce a series of lncRNAs. Among them, an lncRNA called myosin heavy chain-associated RNA transcripts (Myheart or Mhrt) has been shown to be cardiac-specific and abundant in adult hearts. During heart failure, the Brg1-Hdac-Parp chromatin repressor complex prevents Mhrttranscription, which is essential for development of cardiomyopathyopathy [41,53]. Mhrt has been found to protect the heart from cardiac stress by binding to the helicase domain of Brgl and thus decreasing Brgl's association with its target gene, which results in the suppression of cardiac hypertrophy [41]. However, increased levels of stress stimuli have been found to down-regulate Mhrt through the activation of Brgl-Hdac-Parp chromatin complex, which exacerbates cardiac hypertrophy. Also, Mhrt inhibits Brg1 that is a chromatin-remodeling factor stimulated by stress and increases the levels of detrimental genes involved in cardiomyopathy. Because the human heart is also known to express Mhrt that is originated from _Myh7_ loci, it is suggested that Mhrt has its potentially conserved biological function [41].  
Another study by [PERSON] _et al._, sought to discover specific lncRNAs that may be important in heart failure. The study used myocardial-targeted pdk1 knockout (KO) mice on postnatal days 8 and 40. It was shown that 2024 lncRNAs or 4059 lncRNAs were dysregulated at postnatal day 8 or 40, respectively in the KO mice compared to control groups [44]. In addition, using advanced bioinformatic technologies, mitogen-activated protein kinase (MAPK) signaling pathway was found to be a major regulator in heart failure progression. In heart failure patients, four LncRNAs (DGCR5, H19-AS, HOTAIR, and RMRP) in plasma were differentially regulated compared to healthy people (Table 1 and Figure 3). Further analysis revealed that a sense overlap lncRNA called mkk7 was involved in heart failure. The lncRNA mkk7 was downregulated in cardiomyocytes isolated from mice on postnatal day eight in the pdk1 KO mice as compared to the control group. Overall, the study demonstrated a correlation between mkk7 levels and heart failure progression [44].