PKCδ signalling regulates SR-A and CD36 expression and foam cell formation.

AIMS: The formation of foam cells is crucial in the initiation and progression of atherosclerosis. One of the critical steps in foam cell formation is the uptake of low-density lipoprotein (LDL) by macrophages via scavenger receptors (SRs). This study examined the role of protein kinase C (PKC) isoforms on foam cell formation. METHODS AND RESULTS: The effects of short-hairpin RNA (shRNA) and small interfering RNA (siRNA) against classical PKC and novel PKC isoforms were investigated in THP-1-derived macrophages and primary macrophages. The knockdown of PKCδ inhibited oxidized LDL (OxLDL) uptake and intracellular cholesterol accumulation in both cell models. The reduction of PKCδ resulted in decreased expression of SR-A and CD36. Similar conclusions were obtained in examining the effects of a PKCδ inhibitor, rottlerin. Molecular investigation revealed that a decrease in PKCδ inhibited protein kinase B (PKB/Akt) expression and extracellular-signal-regulated kinase (ERK) phosphorylation. Surprisingly, PKCδ-knockdown selectively decreased protein but not the mRNA level of PKCßI and PKCßII. We showed that the inhibition of phosphatidylinositol 3-kinase (PI3K)/Akt upstream of ERK decreased SR-A and CD36 expression; however, the inhibition of ERK or PKCß downstream of ERK attenuated SR-A but not CD36 expression. We further demonstrated that PKCδ could be induced by pro-atherogenic mediators, OxLDL and interferon-γ. Notably, PKCδ, phosphorylated ERK, Akt, and SR-A were highly expressed in human atherosclerotic arteries and CD68-positive macrophages as visualized by immunohistochemical staining. CONCLUSION: Through regulating PI3K/Akt and ERK activity, PKCδ affects SR-A and CD36 expression and foam cell formation. The results suggest PKCδ as a potential target for atherosclerosis therapeutics.

Reversion of left ventricular systolic dysfunction and abnormal stress test: by catheter ablation, in a patient with Wolff-Parkinson-White syndrome from Para-Hisian Kent bundle.

The diagnosis of Wolff-Parkinson-White syndrome is typically reserved for patients who experience ventricular pre-excitation and symptoms that are related to paroxysmal supraventricular tachycardia, such as chest pain, dyspnea, dizziness, palpitations, or syncope. Herein, we report the case of a 38-year-old woman who presented at our outpatient department because of exercise intolerance. Cardiac auscultation revealed a grade 2/6 pansystolic murmur over the left lower sternal border. Twelve-lead electrocardiography showed sinus rhythm at a rate of 76 beats/min, with a significant delta wave. Transthoracic echocardiography revealed abnormal left ventricular systolic function. The results of a thallium stress test were also abnormal. Coronary artery disease was suspected; however, coronary angiography yielded normal results. Electrophysiologic study revealed a para-Hisian Kent bundle and a dual atrioventricular nodal pathway. After radiofrequency catheter ablation was performed, the patient's left ventricular function improved and her symptoms disappeared. In Wolff-Parkinson-White syndrome, left ventricular systolic dyssynchrony can yield abnormal findings on echocardiography and thallium scanning--even in persons who have no cardiovascular risk factors. Physicians who are armed with this knowledge can avoid performing coronary angiography unnecessarily. Catheter ablation can reverse the dyssynchrony of the ventricle and improve the patient's symptoms.

Simultaneous thromboses of double coronary arteries in a young male with antithrombin III deficiency.

In most acute ST-segment elevation myocardial infarction, a single culprit vessel is often found; however, multivessel occlusion, although uncommon, can occur and usually with a poor prognosis, including mortality. We reported a 22-year-old young male who presented to our emergency department because of chest pain after exercise. On physical examination, the cardiac auscultation revealed gallop rhythm without murmur, and the pulmonary auscultation revealed minimal basal moist rales. Other physical examinations were unremarkable. Twelve-lead electrocardiography showed normal sinus rhythm with rate of 96 beats per minute, hyperacute T wave in V1 to V6 and II, III, aVF with reciprocal change in lead I, aVL. He underwent immediate coronary angiography that revealed simultaneous total occlusion of proximal portion of right coronary artery and left anterior descending coronary artery. Successful percutaneous coronary intervention with angioplasty was performed with optimal angiographic result. Although simultaneous total occlusion of double coronary arteries is a rare condition, especially in young group with antithrombin III deficiency, percutaneous coronary intervention and long-term anticoagulant agent are still one of the standard treatments, but the operator should be aware of the hemodynamic change and the importance of mechanical support.

Trastuzumab (Herceptin)-associated cardiomyopathy presented as new onset of complete left bundle-branch block mimicking acute coronary syndrome: a case report and literature review.

Trastuzumab (Herceptin) is well documented in reducing suffering and mortality from breast cancer. The clinically most important side effect of Herceptin is cardiotoxicity, which is reported in 2.6% to 4.5% of patients receiving trastuzumab alone and in as many as 27% of patients when trastuzumab is combined with an anthracycline in metastatic disease. We reported the case of a 50-year-old woman who presented to our emergency department (ED) because of chest pain and shortness of breath. On physical examination, holosystolic murmur over apex could be heard. Pulmonary and abdominal examinations were unremarkable. Twelve-lead electrocardiography showed sinus tachycardia and new onset of complete left bundle-branch block. Emergent transthoracic echocardiography revealed generalized hypokinesia of left ventricle and akinesia over interventricular septum and apex. She subsequently underwent immediate coronary angiography that revealed normal coronary angiography, and left ventriculogram revealed generalized hypokinesia with severe left ventricle dysfunction with ejection fraction of 33%. During right heart catheterization and endomyocardial biopsy, cardiac tamponade developed and was successfully relieved by pericardial window. She was discharged event-free 3 weeks later with conservative treatment. Although new onset of complete left bundle-branch block in a patient with chest pain may be acute coronary syndrome, careful review of medicine history is mandatory to avoid unnecessary procedure and complications.