THYMOSIN BETA-4 (TB4) AND SHORT TRANSMEMBRANE PEPTIDE 1 (STMP1) IN CARDIOVASCULAR DISEASE

Abstract

TB4 is a regenerative and cardioprotective small protein. Using a mass spectrometry-based assay, baseline plasma TB4 was quantified in a local cohort. Plasma TB4 is elevated in female heart failure with preserved ejection fraction patients and is prognostic of mortality, but not in male patients. Potential sources of variability in plasma TB4 was then explored.

To elucidate the molecular mechanism of TB4, rat myocyte culture was pre-treated with anionic boron cluster conjugated synthetic TB4. Label-free quantitative proteomics reveal that HMGB1, a transcription regulator, is elevated with unmodified TB4, but downregulated with modification at the E42/S43 residue.

STMP1 was implicated in mouse heart failure models. To reveal the functional role of STMP1 in the heart, CRISPR-cas9 knockout human iPSC cell lines were made. After induction of cardiomyocyte differentiation, cell lysate was harvested for iTRAQ-based quantitative proteomics. MAGEA4 was downregulated, and ARMCX was upregulated in STMP1 knockout—an observation corroborated by RNAseq.