The Sarcoplasmic Reticulum Ca2+-ATPase (SERCA2) Gene Promoter Activity is Decreased in Response to Severe Left Ventricular Pressure-overload Hypertrophy in Rat Hearts

Left ventricular SERCA2a gene down‐regulation does not parallel ANP gene up‐regulation during post‐MI remodelling in rats

“…This could explain why some NF-MI rats in our study had LV SERCA2a mRNA levels higher than those in some sham-operated rats. In contrast to pressure overload, SERCA2a mRNA levels are reported to be unchanged in volume-overload-induced LV hypertrophy [16,23], in good agreement with the variable decrease in a-MHC gene expression in rats with LVH secondary to aorto-caval fistula [48].…”

“…The triggers of these regulatory processes are elusive, especially regarding the transition from SERCA2a overexpression in mild LVH to decreased SERCA2a expression in more severe LVH. Several regulatory regions have recently been identified in the SERCA2a promoter, including a transcription activation site located between two transcription inhibition sites [16,51]. Severe pressure-overload-induced LVH is required to produce a significant decrease in SERCA2a promoter activity [16].…”

“…Several regulatory regions have recently been identified in the SERCA2a promoter, including a transcription activation site located between two transcription inhibition sites [16,51]. Severe pressure-overload-induced LVH is required to produce a significant decrease in SERCA2a promoter activity [16]. More recently, the transcription factors Sp1 and Sp3 were shown to be involved in this process [52,53], Sp1 gene up-regulation correlating with SERCA2a gene down-regulation [52].…”

“…This explains, at least in part, the decreased SR function. In animals, the decrease in SERCA2a expression is most clear-cut in models of pressure-overload-induced LV hypertrophy and failure [1,2,[14][15][16][17][18][19][20][21][22]. In contrast, SERCA2a expression is unchanged in volume-overload-induced LV hypertrophy [23].…”

Cardiac genes show contextual SWI/SNF interactions with distinguishable gene activities

“…17,22,23 A fetal gene expression program is re-activated concomitant with the development of hypertrophy, while a number of key functional genes are downregulated, which exerts a negative impact on myocardial function. Suppressed expression of genes, including β 1 -adrenergic receptors (β 1 AR), 18 α-MHC, 24,25 sarcoendoplastic reticulum-Ca 2+ ATPase2 (SERCA2A), 26,27 and peroxisome proliferator-activated receptor-α (PPARα), 28 lead to attenuated inotropic reserve mediated by β 1 AR, attenuated contractile function by decreased proportion of α/β isoforms of MHC, dysregulation of (Ca 2+ ) i leading to diastolic and systolic dysfunction, and altered energy metabolism, which is under regulation by PPARα. Studies using genetically modified mouse models have demonstrated a causative role of the molecular remodeling events in myocardial dysfunction and heart failure.…”