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Cardiovascular Diseases (CVDs)

Research on cardiomyocyte dysfunction

The incidence and subsequent social and financial burdens of CVDs are expected to rapidly rise as life expectancy increases and lifestyles change. The Division of Cardiovascular Disease has been trying to find scientific evidence for the prevention and management of CVDs to decrease their prevalence and the resultant mortality. The zebrafish model has been used for study development for decades. Recently, cardiovascular and metabolic diseases were also studied in the zebrafish model owing to its many advantages, particularly its utility in systemic and large-scale approaches to dissect genetic pathways.

Our lab established the Zebrafish Core Facility as part of the future national research infrastructure. The zebrafish facility, inaugurated in September 2013, includes a water tank and a stand-alone fish-housing unit. Currently, 1,000 fish from wild-type and 10 different zebrafish lines are being housed in 150 fish tanks. The laboratory is equipped with a needle puller, incubators, microscopes, and injectors. Additionally, we introduced high-throughput monitoring and MicroZebraLab systems that are expected to provide information on the heartbeat, blood flow, vessel diameter variations, and social behaviours of zebrafish. We established 10 targetgene-specific mutants using the CRISPR/Cas9 genome-editing system that allows researchers to edit genes very precisely, easily, and quickly. This facility resource is available to internal and external researchers. Current projects include developing zebrafish models of CVDs (Fig. 2). We also established an efficient method for zebrafish sperm cryopreservation and in vitro fertilization. Finally, zebrafish fed on a high-fat diet developed dysfunction of lipid metabolism, creating an atherosclerosis model that is important to study CVDs. In conclusion, we have researched CVDs by investigating the effects of several candidate genes on CVDs in the zebrafish model and in vitro cell systems. Through these studies, we expect to be able to identify new therapeutic targets for CVDs.

Zebrafish etv2-CRISPR/Cas9 mutant as a cardiovascular disease model.
Figure1. Zebrafish etv2-CRISPR/Cas9 mutant as a cardiovascular disease model.

Epidemiological studies of CVDs

To prevent and manage CVDs, it is important to develop disease management and treatment guidelines based on scientific evidence. Our institution has established the Korean Acute Heart Failure Registry (KorAHF), the Korea Acute Myocardial Infarction Registry-National Institute of Health (KAMIR-NIH), and the Korean Urban and Rural Elderly Cohort (KURE). In total, 5,625 patients hospitalized for acute heart failure syndromes and 13,623 patients with acute myocardial infarction were enrolled in the KorAHF and KAMIR-NIH registries, respectively. We recruited 3,517 elderly Koreans aged ≥ 65 years from 2012 to 2015 in the KURE study. The subjects were followed continuously till 2017.

Incidence of atrial brillation (AF) in Korea: the National Sample Cohort (2002–2010)

AF is a common arrhythmia shown to be a major independent risk factor for a stroke. However, limited information is available on AF in Korea. We examined the incidence and risk factors of AF and the contribution of comorbidities to the incidence of AF by using a nationwide cohort study.

The National Health Insurance Service-National Sample Cohort database during 2002–2010 was searched for subjects diagnosed with AF. We excluded subjects who were less than 30 years of age or diagnosed with AF during the window period (2002–2004). During a six-year follow-up period, 3,517 subjects (1.7%) developed AF. The incidence rates in men and women aged 30–39 years were 0.82 and 0.55 per 1,000 person-years, respectively; and the incidence rates further increased with age to 13.09 and 11.54 per 1,000 person-years in men and women aged ≥ 80 years, respectively (Fig. 2).
Risk factors for AF were age, sex, body mass index (BMI), hypertension, ischemic heart disease (IHD), and heart failure. After adjusting for variables related to AF, the population attributable fractions for hypertension, IHD, and heart failure were 16.6%, 8.2%, and 5.3%, respectively. The incidence of AF increased with age and was higher in men than in women. The risk of AF was significantly associated with hypertension, IHD, and heart failure. These findings suggest the importance of hypertension management in preventing AF.
 Incidence rate per 1000 person-years of atrial fibrillation (AF) during a 6-year follow-up period according to age and sex

Figure 3. Incidence rate per 1000 person-years of atrial fibrillation (AF)
during a 6-year follow-up period according to age and sex