Cholesterol diet enhances daily rhythm of Pai-1 mRNA in the mouse liver

Sep 14, 2004American journal of physiology. Endocrinology and metabolism

Cholesterol diet strengthens daily patterns of Pai-1 gene activity in mouse liver

AI simplified

Circadian Biology on OpenScience ↗PubMed ↗DOI ↗

Abstract

Hypercholesterolemia significantly upregulated the daily expression of the Pai-1 gene in the mouse liver (P < 0.01).

Myocardial infarction often occurs in the morning, potentially linked to reduced fibrinolytic activity.
Plasminogen activator inhibitor-1 (PAI-1) plays a critical role in regulating fibrinolytic activity.
Hypercholesterolemia is associated with increased PAI-1 activity, which may contribute to atherosclerosis.
Daily expression of clock genes and clock-controlled genes was not significantly impacted by hypercholesterolemia (P > 0.05).
Daily restricted feeding for 4 hours during the day was able to reset the expression of several key genes.
Lesioning the suprachiasmatic nucleus disrupted the daily expression patterns of Per2 and Pai-1.

AI simplified

Myocardial infarction frequently occurs in the morning, a phenomenon in part resulting from the downregulation of fibrinolytic activity. Plasminogen activator inhibitor-1 (PAI-1) is a key factor behind fibrinolytic activity, and its gene expression is controlled under the circadian clock gene in the mouse heart and liver. Hypercholesterolemia has been associated with impaired fibrinolysis due to enhanced PAI-1 activity, which has also been implicated in atherosclerosis. The aim of this study was to decipher whether the Pai-1 gene is still expressed daily with hypercholesterolemia. Hypercholesterolemia (1% cholesterol diet) did not significantly affect the daily expression of clock genes (Per2 and Bmal1) and clock-controlled genes (Dbp and E4bp4) in the liver (P > 0.05); however, daily expression of the Pai-1 gene and Pai-1 promoter regulating factor genes such as Nr4a1 was significantly upregulated (P < 0.01). Daily restricted feeding for 4 h during the day reset the gene expression of Per2, Pai-1, Nr4a1, and Tnf-alpha. Lesion of the suprachiasmatic nucleus, the location of the main clock system, led to loss of Per2 and Pai-1 daily expression profiles. In the present experiments, we demonstrated that hypercholesterolemia enhanced daily expression of the Pai-1, Tnf-alpha, and Nr4a1 genes in the mouse liver without affecting clock and clock-controlled genes. Therefore, the risk or high frequency of acute atherothrombotic events in the morning still seems to be a factor that may be augmented under conditions of hypercholesterolemia.

Full Text

Full text is available at the source.

View full text ↗

Cholesterol diet enhances daily rhythm of Pai-1 mRNA in the mouse liver

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief