Intercalated disc protein Xinβ is required for Hippo-YAP signaling in the heart.

Intercalated discs (ICD), specific cell-to-cell contacts that connect adjacent cardiomyocytes, ensure mechanical and electrochemical coupling during contraction of the heart. Mutations in genes encoding ICD components are linked to cardiovascular diseases. Here, we show that loss of Xinβ, a newly-identified component of ICDs, results in cardiomyocyte proliferation defects and cardiomyopathy.

Loss of MicroRNA-155 protects the heart from pathological cardiac hypertrophy.

Rationale: In response to mechanical and pathological stress, adult mammalian hearts often undergo mal-remodeling, a process commonly characterized as pathological hypertrophy, which is associated with upregulation of fetal genes, increased fibrosis, and reduction of cardiac dysfunction. The molecular pathways that regulate this process are not fully understood.

Objective: To explore the function of microRNA-155 (miR-155) in cardiac hypertrophy and remodeling.

mir-17-92 cluster is required for and sufficient to induce cardiomyocyte proliferation in postnatal and adult hearts.

Rationale: Cardiomyocytes in adult mammalian hearts are terminally differentiated cells that have exited from the cell cycle and lost most of their proliferative capacity. Death of mature cardiomyocytes in pathological cardiac conditions and the lack of regeneration capacity of adult hearts are primary causes of heart failure and mortality. However, how cardiomyocyte proliferation in postnatal and adult hearts becomes suppressed remains largely unknown.

MicroRNA-22 regulates cardiac hypertrophy and remodeling in response to stress.

Rationale: The adult heart is composed primarily of terminally differentiated, mature cardiomyocytes that express signature genes related to contraction. In response to mechanical or pathological stress, the heart undergoes hypertrophic growth, a process defined as an increase in cardiomyocyte cell size without an increase in cell number. However, the molecular mechanism of cardiac hypertrophy is not fully understood.

CIP, a cardiac Isl1-interacting protein, represses cardiomyocyte hypertrophy.

Rationale: Mammalian heart has minimal regenerative capacity. In response to mechanical or pathological stress, the heart undergoes cardiac remodeling. Pressure and volume overload in the heart cause increased size (hypertrophic growth) of cardiomyocytes.

miR-155 inhibits expression of the MEF2A protein to repress skeletal muscle differentiation.

microRNAs (miRNAs) are 21-23-nucleotide non-coding RNAs. It has become more and more evident that this class of small RNAs plays critical roles in the regulation of gene expression at the post-transcriptional level. MEF2A is a member of the MEF2 (myogenic enhancer factor 2) family of transcription factors.

The emerging role of microRNAs as a therapeutic target for cardiovascular disease.

MicroRNAs (miRNAs) are a class of small non-coding RNAs that are endogenously transcribed and processed into approximately 21- to approximately 23-nucleotide products. They are believed to function predominantly as sequence-targeted modifiers of gene expression through inhibition of post-transcriptional processes, including messenger RNA degradation and translational repression. Rapid expansion of functional studies of miRNAs in recent years has established a new paradigm in which miRNAs 'fine-tune' gene expression in complex biologic networks.

MicroRNA-208a is a regulator of cardiac hypertrophy and conduction in mice.

MicroRNAs (miRNAs) are a class of small noncoding RNAs that have gained status as important regulators of gene expression. Here, we investigated the function and molecular mechanisms of the miR-208 family of miRNAs in adult mouse heart physiology. We found that miR-208a, which is encoded within an intron of alpha-cardiac muscle myosin heavy chain gene (Myh6), was actually a member of a miRNA family that also included miR-208b, which was determined to be encoded within an intron of beta-cardiac muscle myosin heavy chain gene (Myh7).

Expression of microRNAs is dynamically regulated during cardiomyocyte hypertrophy.

MicroRNAs (miRNAs) are a recently discovered class of approximately 22-nucleotide regulatory RNAs that post-transcriptionally regulate gene expression. We have recently demonstrated that muscle-specific miRNAs miR-1 and miR-133 play an important role in modulating muscle proliferation and differentiation. Here, we investigate the involvement of miRNAs in cardiac hypertrophy.

Probing the caspase-3 active site by fluorescence lifetime measurements.

The active site of an apoptotic enzyme caspase-3 was characterized by measuring the intrinsic fluorescence of two tryptophan residues. Temperature dependence of the intrinsic fluorescence, the energy homotransfer between the tryptophan residues, and the fluorescence quenching by tetrapeptide inhibitors were investigated by the fluorescence lifetime measurements. It has been observed that the fluorescence lifetimes of caspase-3 in complex with inhibitors were significantly shortened by the electron transfer process.