Norihiro Morikawa

Diagnostic Use of Serum Deoxyribonuclease I Activity as a Novel Early-Phase Marker in Acute Myocardial Infarction

Background—The delayed release of serum cardiac markers such as creatine kinase isoenzyme MB and equivocal early electrocardiographic changes have hampered a diagnosis of acute myocardial infarction (AMI) in the early phase after its onset. Therefore, a reliable serum biochemical marker for the diagnosis of AMI in the very early phase is desirable. Methods and Results—Serum samples were collected from the patients with AMI, unstable angina pectoris, stable angina pectoris, and other diseases. Levels of serum deoxyribonuclease I (DNase I) activity in the patients were determined. An abrupt elevation of serum DNase I activity was observed within approximately 3 hours of the onset of symptoms in patients with AMI, with significantly higher activity levels (21.7±5.10 U/L) in this group compared with the other groups with unstable angina pectoris (10.4±4.41 U/L), angina pectoris (10.8±3.70 U/L), and other diseases (9.22±4.16 U/L). Levels of the DNase I activity in serum then exhibited a marked time-dependent decline within 12 hours and had returned to basal levels within 24 hours. Conclusions—We suggest that serum DNase I activity could be used as a new diagnostic marker for the early detection of AMI.

Aldosterone inhibits endothelial morphogenesis and angiogenesis through the downregulation of vascular endothelial growth factor receptor-2 expression subsequent to peroxisome proliferator-activated receptor gamma

Angiogenesis plays a pivotal role in cardiovascular diseases such as ischemic heart disease, limb ischemia and heart failure, and has recently been shown to mediate various biological activities related to the pathogenesis of these diseases. In the present study, we evaluated the role of aldosterone in angiogenesis. Tube formation assay on Matrigel using human umbilical vein endothelial cells (HUVEC) revealed that aldosterone inhibited endothelial morphogenesis in a manner sensitive to eplerenone, a selective mineralocorticoid receptor antagonist. The anti-angiogenic effect of aldosterone was further confirmed by an in vivo angiogenesis assay using a Matrigel plug model in mice. Reverse transcription-mediated polymerase chain reaction and immunoblotting demonstrated that aldosterone downregulated the expression levels of vascular endothelial growth factor receptor-2 (VEGFR-2) and peroxisome proliferators-activated receptor gamma (PPAR gamma). VEGFR-2 expression was found to be enhanced in response to PPAR gamma activation by troglitazone, and attenuated by GW9662, a specific antagonist of PPAR gamma. In the tube formation assay, endothelial morphogenesis was stimulated by troglitazone, and inhibited by GW9662, indicating that PPAR gamma activation mediates positive regulation of angiogenesis through enhancement of VEGFR-2 expression. These data suggest that aldosterone inhibits angiogenesis through VEGFR-2 downregulation, subsequent to, at least in part, attenuation of PPAR gamma expression. The present findings provide a new insight into the possible therapeutic application of mineralocorticoid receptor blockade to various cardiovascular diseases.

First survey of the three gene polymorphisms (PON1 Q192R, eNOS E298D and eNOS C-786T) potentially associated with coronary artery spasm in African populations and comparison with worldwide data.

Three polymorphisms, Paraoxonase 1 (PON1) Q192R (C/G), endothelial nitric oxide synthase (eNOS) E298D (G/T) and eNOS T‐786C have been suggested to be potentially associated with coronary artery spasm in Japanese patients. Data on worldwide populations are needed to clarify whether these associations could hold true for other populations. However, few data are available especially in Africans, spasm of which has been suggested to be an aetiology of myocardial infarction. Therefore, these polymorphisms were investigated in three Africans, Ovambos (n = 123), Ghanians (n = 118) and Xhosas (n = 96), together with Japanese (n = 96), by using polymerase chain reaction‐restriction fragment length polymorphism analysis. Genotype‐distributions of all these SNPs in African populations were significantly different from those in Caucasians, whereas were similar to those in Japanese population. African populations exhibit relatively higher frequency of spasm‐associated G192 allele in PON1 Q192R being similar to Japanese population, however frequencies of spasm‐associated T298 allele and –C786 allele in SNP eNOS E298D and T‐786C, respectively, were conversely lower in Africans than Caucasians. Although healthy subjects have been recruited in this study, these findings may provide genetic background for elucidation of aetiology of spasm. Copyright