Systems biology approach to exploring the effect of cyclic stretching on cardiac cell physiology

Aging (Albany NY). 2020 Aug 5;12(16):16035-16045. doi: 10.18632/aging.103465. Epub 2020 Aug 5.

Abstract

Although mechanical forces are involved in pressure-overloaded cardiomyopathy, their effects on gene transcription profiles are not fully understood. Here, we used next-generation sequencing (NGS) to investigate changes in genomic profiles after cyclic mechanical stretching of human cardiomyocytes. We found that 85, 87, 32, 29, and 28 genes were differentially expressed after 1, 4, 12, 24, and 48 hours of stretching. Furthermore, 10 of the 29 genes that were up-regulated and 11 of the 28 that were down-regulated after 24 h showed the same changes after 48 h. We then examined expression of the genes that encode serpin family E member 1 (SERPINE1), DNA-binding protein inhibitor 1 (ID1), DNA-binding protein inhibitor 3 (ID3), and CCL2, a cytokine that acts as chemotactic factor in monocytes, in an RT-PCR experiment. The same changes were observed for all four genes after all cyclic stretching durations, confirming the NGS results. Taken together, these findings suggest that cyclical stretching can alter cardiac cell physiology by activating cardiac cell metabolism and impacting cholesterol biosynthesis signaling.

Keywords: cardiac cell; cyclic stretching; functional enrichment; next-generation sequencing.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Chemokine CCL2 / genetics
  • Chemokine CCL2 / metabolism
  • Cholesterol / biosynthesis
  • Energy Metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Inhibitor of Differentiation Protein 1 / genetics
  • Inhibitor of Differentiation Protein 1 / metabolism
  • Inhibitor of Differentiation Proteins / genetics
  • Inhibitor of Differentiation Proteins / metabolism
  • Mechanotransduction, Cellular* / genetics
  • Muscle Spindles / metabolism*
  • Myocytes, Cardiac / metabolism*
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Plasminogen Activator Inhibitor 1 / genetics
  • Plasminogen Activator Inhibitor 1 / metabolism
  • Real-Time Polymerase Chain Reaction
  • Stress, Mechanical
  • Systems Biology*
  • Time Factors
  • Transcriptome

Substances

  • CCL2 protein, human
  • Chemokine CCL2
  • ID1 protein, human
  • Inhibitor of Differentiation Protein 1
  • Inhibitor of Differentiation Proteins
  • Neoplasm Proteins
  • Plasminogen Activator Inhibitor 1
  • SERPINE1 protein, human
  • ID3 protein, human
  • Cholesterol