Identification of osteopontin as a positional and functional candidate gene for cardiac hypertrophy in the SHRSP rat

Osteopontin, a gene situated within a specific region of chromosome 14, has been identified as both a positional and functional candidate gene for cardiac hypertrophy in the SHRSP rat. This trait, marked by a significant increase in left ventricular mass index, is a major risk factor for cardiovascular complications and mortality in cardiometabolic and renal diseases.

Through the use of congenic strains, which introduce trait-associated genetic loci into a control strain, researchers were able to pinpoint the chromosome 14 region linked to this trait. This region was then further examined through cardiac phenotyping and transcriptome profiling at various stages of development. At 5 weeks of age, before hypertension became apparent, SHRSP and WKY.SPGla14a rats demonstrated a significantly higher left ventricular mass index than WKY rats.

Further analysis revealed that the expression of secreted phosphoprotein 1 (Spp1/osteopontin), a gene located within the transferred congenic region, was significantly higher in SHRSP and WKY.SPGla14a rats compared to WKY. This increase in expression was shown to precede the development of increased cardiac mass and the onset of hypertension.

Additionally, overexpression of Spp1 mRNA was observed to significantly increase the size of H9c2 cells, which are involved in cardiac muscle contraction. These findings suggest that Spp1 plays a crucial role in determining left ventricular mass index in the SHRSP rat model of human cardiovascular disease, making it a prime candidate for further research into this condition.