Expression of phospholipase D isozymes in scar and viable tissue in congestive heart failure due to myocardial infarction

Abstract

The phospholipase D (PLD) associated with the cardiac sarcolemmal (SL) membrane hydrolyses phosphatidylcholine to produce phosphatidic acid, an important phospholipid signaling molecule known to influence cardiac function. The present study was undertaken to examine PLD isozyme mRNA expression, protein contents and activities in congestive heart failure (CHF) subsequent to myocardial infarction (MI). MI was induced in rats by occlusion of the left anterior descending coronary artery. At 8 weeks after the surgical procedure, hemodynamic assessment revealed that these experimental rats were at a moderate stage of CHF. Semi‐quantitative reverse transcriptase‐polymerase chain reaction revealed that PLD1 and PLD2 mRNA amounts were unchanged in viable left ventricular (LV) tissue of the failing heart. Furthermore, this technique demonstrated the presence of PLD1 and PLD2 mRNA in the scar tissue. While SL PLD1 and PLD2 protein contents were elevated in the viable LV tissue of the failing heart, SL PLD1 activity was significantly decreased, whereas SL PLD2 activity was significantly increased. On the other hand, although PLD1 protein was undetectable, PLD2 protein and activity were detected in the scar tissue. Our findings suggest that differential changes in PLD isozymes may contribute to the pathophysiology of CHF and may also be involved in the processes of scar remodeling.

Upregulation of Phospholipase D Expression and Activation in Ventricular Pressure-Overload Hypertrophy

“…Thus, our investigations allowed only a casuistic evaluation. Recently Dent et al (34) found that also in the viable LV of the failing rat heart, the sarcolemmal PLD1 and PLD2 protein expressions were elevated; however, in contrast to the present study on the hypertrophied non-failing LV, PLD activation by a phorbol ester was decreased rather than potentiated.…”

“…The expression of both PLD1 and PLD2 was enhanced in the hypertrophied rat LV after aortic banding (present study) and in the failing rat LV after occlusion of a coronary artery (34). In the hypertrophic LV, the upregulation of PLD1 may be, at least in part, responsible for the potentiated activation of PLD caused by α-adrenoceptor and by PKC stimulation because PLD2 is preferentially activated by receptor tyrosine kinase stimulation and is less responsive to PKC activation (9).…”

Downregulation of neuronal sodium channel subunits Nav1.1 and Nav1.6 in the sinoatrial node from volume-overloaded heart failure rat

“…And control animals (n=15) were operated in an identical fashion, but a fistula was not established. Eight weeks after operation, echocardiography was performed to confirm HF formation [10,11] and a subgroup from each treatment arm was randomly selected for hemodynamic study [12].…”

Thematic Review Series: Phospholipases: Central Role in Lipid Signaling and Disease

“…Based on recent reports, cardiac fi brosis is of particular interest. PLD mRNA, protein, and activity levels decrease during congestive heart failure subsequent to myocardial infarction in the scar tissue ( 57 ). The importance of this observation is suggested by a report that inhibition of PLD activity markedly attenuates left ventricular fi brosis, resulting in subsequent improvement in cardiac function ( 64 ).…”

“…PLD1 has been speculated to participate in the process of fi brogenesis in multiple tissue types, including the liver ( 54,55 ), lung ( 56 ), and heart ( 57,58 ). PLD1 is known to be directly connected to autophagy ( 59,60 ), the self-degradative process required for cellular homeostasis that is linked to several forms of liver disease (61)(62)(63).…”