Alteration of mevalonate pathway related enzyme expressions in pressure overload-induced cardiac hypertrophy and associated heart failure with preserved ejection fraction.

Abstract

BACKGROUND:

Abnormalities of the mevalonate pathway, an important cellular metabolic pathway, are common in many diseases including cardiovascular disease. The mevalonate pathway related enzyme expressions in pressure overload-induced cardiac hypertrophy and associated diastolic dysfunction remains largely unknown. This study aims to investigate whether the expression of mevalonate pathway related enzyme is altered during the progression of cardiac hypertrophy and associated diastolic dysfunction induced by pressure overload.

METHODS:

Male Sprague-Dawley (SD) rats were randomly divided into two groups: the suprarenal abdominal aortic coarctation (AAC) group and the sham group.

RESULTS:

Histological and echocardiographic assessments showed that there was a significant cardiovascular remodeling in the AAC group compared with the sham group after 3 weeks post-operatively, and the left ventricular (LV) diastolic function was reduced at 8 and 14 weeks post-operatively in the AAC group, without any change in systolic function during the study. The tissue of the heart and the abdominal aorta proximal to the coarctation showed over-expression of several enzymes, including 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR), farnesyl diphosphate synthase (FDPS), farnesyltransferase-α (FNTA), farnesyltransferase-β (FNTB), geranylgeranyltransferase type I (GGTase-I) and the activation of their downstream proteins was enhanced.

CONCLUSIONS:

AAC induced compensatory LV hypertrophy to decompensatory diastolic dysfunction, accompanied by altered expression of several key enzymes in the mevalonate pathway.

• Authors: Bin Chen, Li-Yun Zhong, Jin-Xiu Yang, Yan-Yun Pan, Fei Chen, Jian Yang, Tao Wu, Shen-Jiang Hu
• Journal: Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology (Cell Physiol Biochem) Vol. 32 Issue 6 Pg. 1761-75 ( 2013) ISSN: 1421-9778 [Electronic] Germany
• PMID: 24356578 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 S. Karger AG, Basel.

Chemical References

• Natriuretic Peptide, Brain
• Hydroxymethylglutaryl CoA Reductases
• Alkyl and Aryl Transferases
• geranylgeranyltransferase type-I
• Geranyltranstransferase
• Farnesyltranstransferase
• Mitogen-Activated Protein Kinase 1
• Mitogen-Activated Protein Kinase 3
• ras Proteins
• rhoA GTP-Binding Protein
• Mevalonic Acid

Topics

• Alkyl and Aryl Transferases (metabolism)
• Animals
• Blood Pressure
• Disease Models, Animal
• Farnesyltranstransferase (metabolism)
• Geranyltranstransferase (metabolism)
• Heart Failure (enzymology, metabolism, pathology)
• Hydroxymethylglutaryl CoA Reductases (metabolism)
• Hypertrophy, Left Ventricular (enzymology, metabolism, pathology)
• Male
• Mevalonic Acid (metabolism)
• Mitogen-Activated Protein Kinase 1 (metabolism)
• Mitogen-Activated Protein Kinase 3 (metabolism)
• Natriuretic Peptide, Brain (metabolism)
• Rats
• Rats, Sprague-Dawley
• Ventricular Pressure
• ras Proteins (metabolism)
• rhoA GTP-Binding Protein (metabolism)