**4. Future directions of large animal model-based cardiovascular research**

#### **4.1 Pig proteomics and the extrapolation to humans**

Recent efforts have been focused on the characterization of experimental animals at the molecular level such as genomics, transcriptomics, and proteomics [35] which revealed the close similarity of proteomics in pigs and humans. Since matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) was first reported in the 1980s, the technologies have been successfully used in genome, proteome, metabolome, and clinical diagnostic research [63]. It is useful in qualitative and quantitative analyses of disease biomarkers in various specimens that lead to not only diagnosis but also risk stratification and guidance in the selection of therapeutic modalities [64]. Linscheid et al. recently performed systematic analyses of cardiac proteomes across cardiac chambers in humans, pigs, and four commonly used animal models and identified and quantified approximately 7,000 proteins, comparing them with respect to cardiac function and mechanisms of diseases [65]. Tamiyakul et al. performed a proteome analysis on the myocardium of the DMD pig model that showed an altered abundance of several proteins such as reduction of myosin-6, which is directly involved in muscle contraction [66]. Müller et al. reported a pig cardiac transcriptome analysis. They assembled 15,926 transcripts, stratified them, and validated the results by complementary mass spectrometry [67]. These attempts to analyze the proteome and transcriptome in animal models and even in humans will play an important role in the future of cardiovascular regenerative medicine. The knowledge of novel heart failure biomarkers may allow a more personalized medicine in the future [68].
