PPARa and cardiomyocytes

BACKGROUND: Acute myocardial infarction (AMI) is a serious cardiovascular disease that adversely affects human health. Circular RNAs (circRNAs) are involved in the pathological and physiological processes of AMI, but the biological mechanism of their involvement and their clinical significance remain unknown. We aimed to identify circRNAs that are significantly associated with morbidity in the peripheral blood of patients with AMI and evaluate their diagnostic utility. METHODS: High-throughput sequencing was used to screen for differentially expressed circRNAs in peripheral blood samples obtained from five patients with AMI and five sex- and age-matched healthy controls...

BACKGROUND: Metabolic cardiomyopathy (MCM), characterized by intramyocardial lipid accumulation, drives the progression to heart failure with preserved ejection fraction (HFpEF). Although evidence suggests that the mammalian silent information regulator 1 (Sirt1) orchestrates myocardial lipid metabolism, it is unknown whether its exogenous administration could avoid MCM onset. We investigated whether chronic treatment with recombinant Sirt1 (rSirt1) could halt MCM progression. METHODS: db/db mice, an established model of MCM, were supplemented with intraperitoneal rSirt1 or vehicle for 4 weeks and compared with their db/ + heterozygous littermates...

Clinically, cardiac dysfunction is a key component of sepsis-induced multi-organ failure. Mitochondria are essential for cardiomyocyte homeostasis, as disruption of mitochondrial dynamics enhances mitophagy and apoptosis. However, therapies targeted to improve mitochondrial function in septic patients have not been explored. Transcriptomic data analysis revealed that the peroxisome proliferator-activated receptor (PPAR) signaling pathway in the heart was the most significantly decreased in the cecal ligation puncture-treated mouse heart model, and PPARα was the most notably decreased among the three PPAR family members...

Pluripotent stem-cell-derived cardiomyocytes (PSC-CMs) provide an unprecedented opportunity to study human heart development and disease, but they are functionally and structurally immature. Here, we induce efficient human PSC-CM (hPSC-CM) maturation through metabolic-pathway modulations. Specifically, we find that peroxisome-proliferator-associated receptor (PPAR) signaling regulates glycolysis and fatty acid oxidation (FAO) in an isoform-specific manner. While PPARalpha (PPARa) is the most active isoform in hPSC-CMs, PPARdelta (PPARd) activation efficiently upregulates the gene regulatory networks underlying FAO, increases mitochondrial and peroxisome content, enhances mitochondrial cristae formation, and augments FAO flux...

Peroxisome proliferator-activated receptor α (PPARα), a ligand-activated nuclear receptor critical for systemic lipid homeostasis, has been shown closely related to cardiac remodeling. However, the roles of cardiomyocyte PPARα in pressure overload-induced cardiac remodeling remains unclear because of lacking a cardiomyocyte-specific Ppara-deficient (PparaΔCM ) mouse model. This study aimed to determine the specific role of cardiomyocyte PPARα in transverse aortic constriction (TAC)-induced cardiac remodeling using an inducible PparaΔCM mouse model...

Diabetes contributes to cardiovascular complications and the pathogenesis of cardiac remodeling that can lead to heart failure. We aimed to evaluate the functional role of LAZ3 in diabetic cardiomyopathy (DCM). Streptozotocin (STZ) was used to induce a diabetic mouse model. Three months after induction, the mice were subjected to retro-orbital venous plexus injection of adeno-associated virus 9 (AAV9) that overexpressed LAZ3. Six weeks after the infection, mouse hearts were removed to assess the degree of cardiac remodeling...

Here we studied the impact of 5-aminoimidazole-4-carboxamide riboside (AICAR), a well-known AMPK activator, on cardiac metabolic adaptation. AMPK activation by AICAR was confirmed by increased phospho-Thr(172)-AMPK and phospho-Ser(79)-ACC protein levels in HL-1 cardiomyocytes. Then, cells were exposed to AICAR stimulation for 24 h in the presence or absence of the AMPK inhibitor Compound C, and the mRNA levels of the three PPARs were analyzed by real-time RT-PCR. Treatment with AICAR induced gene expression of all three PPARs, but only the Ppara and Pparg regulation were dependent on AMPK...

Compromised cardiac fatty acid oxidation (FAO) induced energy deprivation is a critical cause of cardiac dysfunction in sepsis. Acyl-CoA thioesterase 1 (ACOT1) is involved in regulating cardiac energy production via altering substrate metabolism. This study aims to clarify whether ACOT1 has a potency to ameliorate septic myocardial dysfunction via enhancing cardiac FAO. Transgenic mice with cardiomyocyte specific expression of ACOT1 (αMHC-ACOT1) and their wild type (WT) littermates were challenged with Escherichia coli lipopolysaccharide (LPS; 5 mg/kg i...

Di(2-ethylhexyl)phthalate (DEHP) is the most common plasticizer in plastic devices of everyday use. It is a ubiquitous environmental contaminant and primarily known to impair male gonadal development and fertility. Studies concerning the long-term effects of prenatal DEHP exposure on certain diseases [The Developmental Origins of Health and Disease paradigm (DOHaD) hypothesis] are scarce although it is proven that DEHP crosses the placenta. Rising environmental pollution during the last centuries coincides with an increasing prevalence of cardiovascular and metabolic diseases...

OBJECTIVE: To analyze whether genetic variants of PPARA are associated with the development of stage C heart failure. METHODS: We analyzed the distribution of the rs1800206, rs4253778 and rs135551 polymorphisms in genomic DNA extracted from peripheral blood cells of 534 patients in different heart failure stages and 63 healthy individuals. The mRNA expression of the peroxisome proliferator-activated receptor (PPAR)α target genes long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) and medium-chain acyl-CoA dehydrogenase (MCAD) was measured in myocardial biopsies of a subgroup of stage B and C patients...

Peroxisome proliferator activated receptors (PPARs) belong to a subfamily of transcription nuclear factors. Three isoforms of PPARs have been identified: alpha, beta/delta and gamma, encoded by different genes and distributed in various tissues. They play important roles in metabolic processes like regulation of glucose and lipid redistribution. They also have anti-atherogenic, anti-inflammatory as well as anti-hypertensive functions. In hypertension-induced cardiac hypertrophy, both PPARa and PPARg activation reveal cardio-protective effect...