Yoshihiko Kakinuma, MD, PhD

JAHA: Tell us about the key findings from your recent article in JAHA.

Dr. Kakinuma: The non-neuronal cardiac cholinergic system producing extremely more ACh by ventricular cardiomyocytes plays a beneficial role in protecting cardiomyocytes against myocardial infarction. The key mechanism is expected to render cardiomyocytes utilize more glucose and less oxygen. 

JAHA: What are the major implications of this work?

Dr. Kakinuma: Non-neuronal cardiac cholinergic system plays a role in decreasing oxygen demand by cardiomyocytes and in accelerating angiogenesis.

JAHA: How did you get the idea to do this study?

Dr. Kakinuma: From our previous study showing that cardiomyocytes synthesize ACh of their own.

JAHA: What was your biggest obstacle in completing this study?

Dr. Kakinuma: The concept that cardiomyocytes synthesize ACh is not yet well known and accepted by

others.

JAHA: What was your most unexpected finding?

Dr. Kakinuma: This engineered heart, i.e., a ChAT overexpressing heart, is resistant to no flow conditions in Langendorff apparatus and fairly easy to restart the ventricular beating after reperfusion.

JAHA: What do you plan to do next, based on these current findings?

Dr. Kakinuma: The cellular mechanisms of this non-neuronal cardiac cholinergic system should be profoundly clarified. 

To read Dr. Kakinuma's full article, click here

Profile originally published March 5, 2013

Alka Kanaya, MD

JAHA: Tell us about the key findings from your recent article in JAHA.

Dr. Kanaya: We found that brachial artery flow mediated dilation (FMD) results differed from endothelial function biomarkers for those with pre-diabetes.  While biomarkers of endothelial function (PAI-1, E-selectin, sICAM-1, and vWF) were more uniform in association with glucose levels with higher levels of biomarkers associated with higher glucose levels.  However, the pattern of association with FMD was different—with the pre-diabetes IFG group having higher FMD levels than those with normal or diabetic glucose levels. This was most notable in whites with normal BMI.

JAHA: What are the major implications of this work?

Dr. Kanaya: This discordance between FMD and biomarker results raises the possibility of differential effects of insulin signaling in the endothelium vs. the skeletal muscles or other organs. It may also give us some clues about why some studies have found harmful associations between IFG and future events while others have not. 

JAHA: How did you get the idea to do this study?

Dr. Kanaya: I am interested in studying what factors explain higher prevalence of diabetes in ethnic minority groups vs. European white populations. We are studying South Asians in a prospective cohort study to determine etiologic and prognostic factors associated with diabetes and CVD. Endothelial function was a novel aspect worth studying in South Asians and comparing them to other US ethnic groups.

JAHA: What was your biggest obstacle in completing this study?

Dr. Kanaya: The most difficult part of this study was to understand and explain the novel findings with the differential effects observed by the FMD and the endothelial biomarkers for the IFG group.

JAHA: What was your most unexpected finding?

Dr. Kanaya: See above.

JAHA: What do you plan to do next, based on these current findings?

Dr. Kanaya: We are conducting a larger prospective cohort of 900 South Asians currently (called the Mediators of Atherosclerosis in South Asians Living in America study) which has been created to be parallel in methods and measures to the MESA study. We plan to remeasure endothelial function in this larger study to confirm our original findings.  We will also be examining prospective associations of endothelial function with diabetes incidence in both MESA and MASALA. 

JAHA: What do you like to do in your free time?  

Dr. Kanaya: I like to travel internationally with my family, cook and practice yoga.

JAHA: What is your favorite sports team or musical group? 

Dr. Kanaya: The San Francisco 49ers, Favorite band is U2.

To read Dr. Kanaya's full article, click here

Profile originally published February 26, 2013

Tatsuya Iso, MD, PhD

JAHA: Tell us about the key findings from your recent article in JAHA.

Dr. Iso: PPARg induces expression of FABP4 and FAT/CD36 in capillary endothelial cells to promote FA transport into heart. This system is activated in the postprandial state after prolonged fasting.

JAHA: What are the major implications of this work?

Dr. Iso: Our findings identify capillary endothelium as promising target cells for controlling metabolism of energy substrates in the heart. That is, our demonstration in vivo opens a new research area on the role of trans-endothelial material transport system for the treatment and prevention of cardio-metabolic disease, such as heart failure and metabolic syndrome.

JAHA: How did you get the idea to do this study?

Dr. Iso: We found that FABP4 is strongly expressed in capillary endothelial cells, by immunohistochemistry. FABP4 is cytosolic fatty acid chaperon and one of the most famous PPARg target genes. These findings led me to come up with the idea.

JAHA: What was your biggest obstacle in completing this study?

Dr. Iso: While we were working on this project, a similar study was published in Journal of Clinical Investigation 2009 by Kanda et al.  Adding new data and new story was tough.

JAHA: What was your most unexpected finding?

Dr. Iso: Uptake of ¹²⁵I-BMIPP in hearts was comparable between wild-type and endothelial PPARg KO mice during fasting. We expected remarkable difference. We finally found difference of fatty acid uptake after olive oil gavage.

JAHA: What do you plan to do next, based on these current findings?

Dr. Iso: We will estimate function of endothelial FABP4 and FAT/CD36 by generating endothelial-specific KO mice.

JAHA: What do you like to do in your free time?

Dr. Iso: I play with my kids. Ski,skate, watching movies, etc.

JAHA: What is your favorite sports team or musical group?

Dr. Iso: Lakers when I used to live in Los Angeles. Now, Japan national football team.

To read Dr. Iso's full article, click here

Profile originally published February 19, 2013

Steven P. Dunn, PharmD

JAHA: Tell us about the key findings from your recent article in JAHA.

Dr. Dunn: Our major findings are twofold: One, that the analysis of proton pump inhibitor (PPI) use in the CREDO population whereby the antiplatelet efficacy of clopidogrel may be interfered with, is by and large consistent with previously published randomized, controlled trials such as TRITON and PLATO. Second, that in a randomized, controlled trial of single antiplatelet therapy with aspirin-only versus clopidogrel-only (CAPRIE), PPI use significantly impacted the efficacy of clopidogrel, but not aspirin (p-value for interaction 0.047).

JAHA: What are the major implications of this work?

  
Dr. Dunn: The CREDO data is largely reassuring in the interventional cardiology arena in combination with previously published data. In fact, I think this data set nicely illustrates what we’ve largely seen as concerning signals in observational studies may just reflect confounded data as PPI use “worsened” adverse cardiovascular event rates in both the clopidogrel and placebo 1-year primary endpoint. The CAPRIE data suggests that the PPI drug interaction may be more significant in patients receiving single antiplatelet therapy with clopidogrel.

JAHA: How did you get the idea to do this study?

  
Dr. Dunn:  I was fortunate to have access to some of the individuals who had worked on the CREDO and CAPRIE clinical trial programs and spoke early-on to people within Sanofi and BMS. When the mechanistic potential for this interaction was first described, it seemed logical to me that the randomized data sets would be valuable information to examine, especially when the observational and registry data begin to emerge that this was potentially a serious issue. Fortunately, these two trials had the foresight to capture all concomitant medication use.

JAHA: What was your biggest obstacle in completing this study?

  
Dr. Dunn: It was very difficult to merge and combine the findings from two disparate clinical trials which essentially concluded opposite findings. While this makes for good contrast, it was difficult to rationalize how this could be possible and make a cohesive manuscript.

JAHA: What was your most unexpected finding?

  
Dr. Dunn: The data from CAPRIE were very unexpected to us. To our knowledge, this is the only data from a randomized, controlled trial which demonstrates harm in patients receiving both PPI therapy and clopidogrel versus a comparator.

JAHA: What do you plan to do next, based on these current findings?

  
Dr. Dunn:  I think it would be very valuable to obtain more information about patients taking single antiplatelet therapy with clopidogrel only and whether the interaction is more significant in this particular population of patients. This occurs often, for example, in ischemic stroke prevention.

JAHA: What do you like to do in your free time?

  
Dr. Dunn:  I enjoy spending time with my family and am very busy keeping up with my two-and-a-half year old daughter. Outside of that, I “dabble” in technology and more outdoorsy stuff like hiking, mountain biking, golfing, and “technical” outdoors activities like photography.

JAHA: What is your favorite sports team or musical group?

  
Dr. Dunn:  I am a Western Pennsylvania native so of course I am a Pittsburgh Steelers fan!

To read Dr. Dunn's full article, click here

Profile originally published February 12, 2013

Kathryn A. Britton, MD

JAHA: Tell us about the key findings from your recent article in JAHA.

Dr. Britton: Thoracic periaortic adipose tissue (TAT) is a type of ectopic fat that surrounds the aorta, and has been postulated to have a local toxic effect on the vasculature.  We examined categories of individuals discordant for periaortic and visceral fat in order to better understand the potential specificity of the association of different fat depots with cardiometabolic risk factors.  We found that high TAT was uniquely associated with a higher prevalence of cardiovascular disease, smoking, and low-HDL.

JAHA: What are the major implications of this work?

Dr. Britton: Our findings suggest that individuals with high TAT, even in the absence of high VAT, are characterized by a uniquely adverse cardiometabolic profile.

JAHA: How did you get the idea to do this study?

Dr. Britton: We were interested in establishing the unique risk factor correlates of high thoracic periaortic fat. 

JAHA: What was your biggest obstacle in completing this study?

Dr. Britton: Thoracic periaortic and visceral fat are highly correlated which makes it more challenging to disentangle the specific associations of TAT versus visceral fat with cardiometabolic risk factors.  Thus, we specifically looked at discordant categories to better capture the unique associations of high TAT versus high visceral fat. 

JAHA: What was your most unexpected finding?

Dr. Britton: We were surprised and intrigued to find that men with high thoracic periaortic fat in the absence of high VAT had a higher prevalence of current smoking.  This finding, taken in conjunction with previous findings that thoracic periaortic fat is associated with peripheral artery disease (for which smoking is a major risk factor) and that smoking appears to influence the biology of adipose tissue, will be interesting to pursue in further experimental and observational studies. 

JAHA: What do you plan to do next, based on these current findings?

Dr. Britton: We are interested in looking at changes in TAT over time since many of the individuals in this study are undergoing follow-up CT scans six years later.  In addition, we are interested in examining the association of TAT with other manifestations of cardiovascular disease.  We are also interesting in performing prospective studies examining the association of TAT with different health outcomes over time. 

JAHA: What do you like to do in your free time?

Dr. Britton: I enjoy spending time with my family and friends, and especially enjoy outdoor activities, such as running, walking, and cross-country skiing.  I also enjoy traveling and most recently spent two weeks in Turkey. 

JAHA: What is your favorite sports team or musical group?

Dr. Britton: Although I have lived in Boston for the past 10 years, I was born and raised in New York, and am a longstanding NY Yankee fan. 

To read Dr. Britton's full article, click here

Profile originally published February 5, 2013

Karen Siu Ling Lam, MD

JAHA: Tell us about the key findings from your recent article in JAHA.

Dr. Lam: In 1847 Chinese healthy subjects with no known cardiovascular diseases (heart disease or stroke) we found that a high level of adipocyte fatty acid binding protein (A-FABP) in their blood could predict whether they would develop cardiovascular diseases in 12 years. Their risk was increased by 50% for every unit increase in log-transformed A-FABP level, even after taking into consideration the effect of known cardiovascular risk factors like high blood pressure or cholesterol, diabetes and obesity. It should be noted that A-FABP is a hormone released from the fat cells and inflammatory cells with its blood level being elevated in overweight or obese subjects.

JAHA: What are the major implications of this work?

Dr. Lam: The implications are that A-FABP, which has been shown to be associated with increased cardiovascular diseases in animals, probably also contributes to the development of these diseases in humans. Furthermore, we have shown that measuring its level in our blood can potentially help to identify who are at increased risk of cardiovascular diseases and therefore should receive more intensive preventive measures, including healthy life-style and medications to control the known cardiovascular risk factors. Its use as a “risk marker” in this regard is additive to that of “C-reactive protein”, a marker already used in clinical practice to predict the risk of heart disease and stroke.

JAHA: How did you get the idea to do this study?

Dr. Lam: This is the continuation of our research on A-FABP since 2006 when we first demonstrated its presence in the human circulation and its association with obesity and other atherosclerotic risk factors in humans (Clin Chem 2006). We subsequently demonstrated that a high blood level of A-FABP was associated with atherosclerotic changes in the carotid arteries which supply the brain (ATVB 2007), and could predict the development of the metabolic syndrome (Circulation 2007) and type 2 diabetes (Diabetes Care 2007), two conditions which predispose to cardiovascular diseases. A high level of A-FABP also predicted early death after stroke (Neurology 2011). We therefore investigated whether it could predict the development of cardiovascular disease in the subjects in the Hong Kong Cardiovascular Risk Factors Prevalence Study (CRISP) that we have been following up for 12 years.

JAHA: What was your biggest obstacle in completing this study?

Dr. Lam: The greatest difficulty was in getting the study subjects to return for follow-up assessment repeatedly during the 12 years. This was achieved through the patience and dedication of our research nurses and doctors.

JAHA: What was your most unexpected finding?

Dr. Lam: Our most unexpected finding was that the blood level of adiponectin, another hormone from the fat cells which showed some protection against cardiovascular diseases in animal studies, did not show any suggestion of a protective effect in our study.

JAHA: What do you plan to do next, based on these current findings?

Dr. Lam: We plan to collaborate with other centers to establish A-FABP as a predictive marker of cardiovascular disease for clinical use.

JAHA: What do you like to do in your free time?

Dr. Lam: I enjoy jogging, hiking and reading.

JAHA: What is your favorite sports team or musical group?

Dr. Lam: Not applicable.


To read Dr. Lam's full article, click here
Profile originally published January 29, 2013