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Cardiac Mitochondrial Integrity Is Regulated by CR6-interacting Factor 1 in the Heart.

Seon Ah JIN ; Young Dal LEE ; Jung Yeon YOON ; Sun Kyeong KIM ; Kye Taek AHN ; Soo Jin PARK ; Jun Hyung KIM ; Jae Hyeong PARK ; Jae Hwan LEE ; Si Wan CHOI ; In Whan SEONG ; Jin Ok JEONG

Journal of the Korean Society of Hypertension.2012;18(3):117-125. doi:10.5646/jksh.2012.18.3.117

BACKGROUND: The major cause of metabolic syndrome and diabetes is reduced cellular performances in fuel metabolism, but the underlying pathways and mechanisms are not completely understood. Dysregulation of energy homeostasis can lead to metabolic disturbances and it predisposes diabetes, cardiovascular disease, aging, and cancer. CR6-interacting factor 1 (CRIF1) contacts coiled-coil domain that is required for both genomic stability and mitochondrial integrity. We performed this study to determine the role of CRIF1 on the mice hearts. METHODS: CRIF1-deficient mouse was embryonic lethal and we made heart specific CRIF1-deficient mouse using Cre-loxP system. We made thoracotomy and directly injected adeno-Cre virus into the heart of CRIF1-loxP mice. Beta-gal virus was used as a control. RESULTS: Serial echocardiography showed decreased left ventricular ejection fraction and fractional shortening in the CRIF1-deficient mice at four and seven weeks later compared to wild type mice (p < 0.05). H&E showed increased myocardial inflammation in the CRIF1-deficient mice. Terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling staining and LC3 staining showed increased apoptosis and autophage in CRIF1-deficient mice compared with wild type (p < 0.01). Electron microscopy revealed that the mitochondria in CRIF1-deficient cardiomyocytes showed abnormal morphogenesis. For example, the cells showed excessively fragmented mitochondria, intracristal swelling, and thinning of myocardial fiber. The stability of mitochondrial complexes in CRIF1-deficient cells showed marked derangements. CONCLUSIONS: CRIF1 is required for maintenance of normal mitochondrial function and modulate apoptosis and autophagy in the heart.
Aging ; Animals ; Apoptosis ; Autophagy ; Cardiovascular Diseases ; Cell Cycle Proteins ; DNA Nucleotidylexotransferase ; Echocardiography ; Genomic Instability ; Heart ; Heart Failure ; Homeostasis ; Inflammation ; Mice ; Microscopy, Electron ; Mitochondria ; Mitochondria, Heart ; Morphogenesis ; Myocytes, Cardiac ; Stroke Volume ; Thoracotomy ; Viruses

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Effect of Small Hairpin RNA Molecules Targeting Angiotensin-converting Enzyme Gene in Spontaneously Hypertensive Rats.

Young Mi HONG ; Hye Ryon LEE ; Kwan Chang KIM

Journal of the Korean Society of Hypertension.2012;18(3):105-116. doi:10.5646/jksh.2012.18.3.105

BACKGROUND: Interfering RNA (iRNA) represents a recent breakthrough in effective blocking of the target genes in mammalian cells. Angiotensin-converting enzyme (ACE) has been shown to play an important role in the pathogenesis of hypertension. The purposes of this study were to investigate the effects on blood pressure, myocardial hypertrophy and gene expressions of iRNA targeting ACE. METHODS: Twelve week old male Wistar-Kyoto rats were grouped as follows: control group (C group), spontaneously hypertensive rat (SHR) group (H group), and ACE-iRNA group (A group) in which SHR was treated with recombinant lentiviral vectors carrying small hairpin RNA targeting ACE. Reverse transcription-polymerase chain reaction and western blot analysis of ACE, endothelin (ET)-1, angiotensin (AT) II receptor type 1A, neutrophil cytosolic factor, caspase 3, Bax, and Bcl-2 were performed in the heart tissues. Serum AT, ACE, and high sensitive-C reactive protein were estimated. RESULTS: Systolic blood pressure was significantly decreased in the A group compared with the H group in weeks 3 and 5. Serum AT level was significantly lower on day 1, weeks 3 and 5 after ACE-iRNA treatment. ACE protein contents were significantly lower after ACE-iRNA treatment in week 5. ET-1 and Bcl-2 protein contents were significantly lower after ACE-iRNA treatment in weeks 3 and 5. Bax protein contents were significantly lower after ACE-iRNA treatment in week 3. CONCLUSIONS: Recombinant lentiviral vectors carrying shRNA targeting ACE prevented hypertension. Serum AT and gene expressions such as ACE, ET-1, Bax, and Bcl-2 were significantly decreased after ACE-iRNA treatment.
Angiotensins ; Animals ; bcl-2-Associated X Protein ; Blood Pressure ; Blotting, Western ; Caspase 3 ; Cytosol ; Endothelins ; Gene Expression ; Heart ; Humans ; Hypertension ; Hypertrophy ; Lentivirus ; Lifting ; Male ; Neutrophils ; Rats ; Rats, Inbred SHR ; RNA ; RNA Interference ; RNA, Small Interfering

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Physician's Awareness and Education for Patient on Life Style Modification and Home Blood Pressure Monitoring Recommended in Hypertension Guideline.

Do Young KIM ; Sung Hea KIM ; Hyun Joong KIM ; Sang Man JUNG ; Kyu Hyung RYU

Journal of the Korean Society of Hypertension.2012;18(3):97-104. doi:10.5646/jksh.2012.18.3.97

BACKGROUND: It is important to understand physicians' awareness and knowledge on hypertension guideline to comprehend physician oriented barrier against proper hypertension management. Current guidelines emphasize on the role of home blood pressure monitoring. The aim of this study is to investigate the level of awareness and knowledge of Korean physicians on home blood pressure monitoring recommended in current guideline. METHODS: A questionnaire survey asking home blood pressure measurement, as well as prehypertension and life style modification, was conducted among 36 primary physicians and 25 residents of a tertiary medical center. RESULTS: Except the limitation alcohol intake (80.3%), the physicians demonstrated above 90% of agreement with other contents of life style modification recommended by published guidelines (salt restriction, stop smoking, weight loss, and regular aerobic exercise). Majority (77.7%) of primary physicians recommend home blood pressure measurement to their patients. Significantly primary physicians were likely to recommend home blood pressure monitoring than residents (48% vs. 77.7%, p = 0.027). But both physicians and residents show poor compliance to home blood pressure monitoring guideline in the point of blood pressure measuring (12% vs. 19.4%, p > 0.05). But most of participants are aware of adverse effect of prehypertension (88.5%) and the need of its treatment (96.7%). CONCLUSIONS: This result suggest screening alcohol use disorder and brief counseling by physicians should be encouraged as a part of hypertension management and promoting physicians to equip the correct knowledge of home blood pressure measuring recommended in guideline is warranted.
Blood Pressure ; Blood Pressure Monitoring, Ambulatory ; Compliance ; Counseling ; Humans ; Hypertension ; Life Style ; Mass Screening ; Prehypertension ; Surveys and Questionnaires ; Smoke ; Smoking ; Weight Loss

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Pharmacokinetic and Pharmacodynamic Study Determines Factors Affecting Blood Pressure Response to Valsartan.

Jin Man CHO ; Sung Vin YIM ; Hui JIN ; Il Suk SOHN ; Hui Jeong HWANG ; Chang Bum PARK ; Eun Sun JIN ; Chong Jin KIM

Journal of the Korean Society of Hypertension.2012;18(3):88-96. doi:10.5646/jksh.2012.18.3.88

BACKGROUND: Valsartan is an angiotensin II receptor blocker and is used for patient with hypertension. Although response to valsartan varies each individual, there is no study about factors affecting the variability of valsartan response. METHODS: To investigate the effects of valsartan on the baseline characteristics of blood pressure, single group, open label, pre- and post-comparison clinical study was conducted. Total 21 male Korean volunteers were enrolled. Each subject was administered no drugs in first period and valsartan 80 mg (Diovan HCT) in second period. For pharmacodynamic analysis, 24 hours blood pressure changes were monitored by ambulatory blood pressure monitoring. Twenty-four hour blood pressure changes were matched to valsartan concentration and analyzed by correlation analysis. Changes in blood pressure pattern were also analyzed. Subjects were divided into responder, non-responder, and reverse responder according to pre- and post- 24 hours blood monitoring results. For determination of pharmacokinetic parameters, plasma concentration of valsartan was measured by a validated ultra-performance liquid chromatography-tandem mass spectrometry method. Pharmacokinetic parameters including area under the plasma concentration versus time curve from 0 hour to the last measurable concentration (AUCt), area under the plasma concentration versus time curve extrapolated to infinity, maximum plasma concentration (Cmax), and time required to reach maximum plasma concentration (Tmax) were calculated by noncompartmental models in the BA-CALC 2008 program ver. 1.0.0. RESULTS: There were no significant associations between blood pressure changes and pharmacokinetic parameters of valsartan. Blood pressure pattern change analysis showed significant results. For AUCt, total amount of absorbed valsartan was 25,808 +/- 6,863.0 ng.hr/mL, 20,683 +/- 8,782.7 ng.hr/mL, and 12,502 +/- 5,566.6 ng.hr/mL in responder, non-responder, and reverse responder, respectively (p = 0.041). In C max, maximum concentration of valsartan was 4,314 +/- 1,522.6 ng/mL, 2,588 +/- 1,273.9 ng/mL, and 2,056 +/- 1,075.5 ng/mL, respectively. CONCLUSIONS: These results showed that response to valsartan was not associated with blood concentration in healthy volunteers and changes in blood pressure patterns to valsartan might be associated with the amount of drugs which are absorbed to subjects.
Blood Pressure ; Blood Pressure Monitoring, Ambulatory ; Humans ; Hypertension ; Male ; Mass Spectrometry ; Plasma ; Receptors, Angiotensin ; Tetrazoles ; Valine ; Valsartan

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Blood Pressure Variability and Vascular Dysfunction in Essential Hypertension.

Kenji OKUMURA ; Xian Wu CHENG

Journal of the Korean Society of Hypertension.2012;18(3):75-87. doi:10.5646/jksh.2012.18.3.75

There are several aspects of blood pressure. Clinically, how to best assess blood pressure average and variability is still a matter of the ongoing debate. Besides office blood pressure, we must pay more careful attention focused on hypertension with blood pressure fluctuation. Impaired endothelial function is intimately associated with the development of hypertension and atherosclerosis. In this review, we describe the relation between endothelial dysfunction and hypertension, the effect of gene polymorphism on endothelial dysfunction, the effects of antihypertensive agents and dietary supplementation on impaired endothelial function in hypertension. In order to predict the future atherosclerosis and cardiovascular events in subjects with hypertension, the adequate assessment of endothelial function is one of the most reliable markers. Furthermore, we discuss the close relationship between blood pressure variability and endothelial function. Blood pressure variability during a day or a week is an important, new risk factor for cardiovascular disease and restoring impaired endothelial function might be a target to prevent blood pressure variation and future cardiovascular events.
Antihypertensive Agents ; Atherosclerosis ; Blood Pressure ; Cardiovascular Diseases ; Dietary Supplements ; Hypertension ; Nitric Oxide ; Nitric Oxide Synthase Type III ; Risk Factors

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Changes in Carotid Intima-media Thickness and Left Ventricular Mass by Control of Blood Pressure and Hyperlipidemia in Hypertensive Patients.

Byung Joo SUN ; Duk Hyun KANG ; Gyung Min PARK ; Yong Giun KIM ; Ki Won HWANG ; Sung Won CHO ; Yoo Ri KIM ; Dae Hee KIM ; Jong Min SONG ; Jae Kwan SONG

Journal of the Korean Society of Hypertension.2011;17(4):177-184. doi:10.5646/jksh.2011.17.4.177

BACKGROUND: Hypertensive patients often present with carotid atherosclerosis, and especially those with left ventricular hypertrophy (LVH) are known to have twice the prevalence of carotid atheroma. The aims of this study were to evaluate the changes in the severity of carotid atherosclerosis and left ventricular (LV) mass by control of blood pressure (BP) and hyperlipidemia in hypertensive patients. METHODS: A total of 87 treated hypertensive patients who had been diagnosed as stage 2 hypertension on Joint National Committee 7 classification in past 1 year or LVH on electrocardiographic criteria were enrolled. Both at baseline and the end of study, repetitive measurements of carotid intima-media thickness (IMT) and LV mass indexed by body surface area were performed. Measurement of carotid IMT was conducted at bilateral sides of distal common carotid artery. RESULTS: After the follow-up period of mean 16-months, there were significant lowering in systolic and diastolic BP, respectively (144.6 +/- 19.2 to 131.3 +/- 13.6 mm Hg, p < 0.001; 87.5 +/- 11.3 to 79.6 +/- 9.4 mm Hg, p < 0.001). Carotid IMT showed no significant change (0.75 +/- 0.18 to 0.76 +/- 0.18 mm, p = 0.310). Although there was significant reduction in LV mass index (107.9 +/- 22.0 to 101.0 +/- 18.4 g/m2, p < 0.001), it was not correlated with the changes in carotid IMT (r = 0.141, p = 0.197). CONCLUSIONS: Anti-hypertensive therapy combined with statin if indicated did not show significant reduction in atherosclerotic burden of carotid artery, but it seemed to prevent further progression in hypertensive patients. Decrement in LV mass achieved by BP control was not correlated with changes in carotid IMT.
Atherosclerosis ; Blood Pressure ; Body Surface Area ; Carotid Arteries ; Carotid Artery Diseases ; Carotid Intima-Media Thickness ; Electrocardiography ; Follow-Up Studies ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Hyperlipidemias ; Hypertension ; Hypertrophy, Left Ventricular ; Joints ; Plaque, Atherosclerotic ; Prevalence

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Relationship between Clinical Factors Including Physical Activity and Job Category and Masked Effect Defined by Ambulatory Blood Pressure Monitoring.

Yu Mi KIM ; Hyung Min LEE ; Joo Youn SEO ; Yeon Soo KIM ; Bae Ken KIM ; Mi Kyung KIM ; Bo Youl CHOI ; Jin Ho SHIN

Journal of the Korean Society of Hypertension.2011;17(4):166-176. doi:10.5646/jksh.2011.17.4.166

BACKGROUND: Masked hypertension is well known for its poor cardiovascular outcome. But clinical clues related to the masked hypertension and/or masked effect (ME) are rarely known. Physical activity and/or job stress are related to increased daytime blood pressure (BP). This study is to identify whether ME is caused by physical activity and/or job category. METHODS: Physical activity using Actical and masked effect by clinic BP and ambulatory BP monitoring were applied to 167 person for this study. RESULTS: Age of the subjects was 54.9 +/- 9.6 and 74 subjects were female (57.4%). Field worker was 81 (48.5%) and office worker was 86 (51.5%). Clinic BP was 125.8 +/- 14.3 mmHg / 79.8 +/- 10.9 mmHg in male and 119.0 +/- 14.0 mmHg / 74.2 +/- 8.9 mmHg in female (p = 0.03). Daily energy expenditure representing physical activity was 1,831.1 +/- 420.4 kcal. ME for systolic BP was 11.0 +/- 11.1 mmHg and ME for diastolic BP was 3.9 +/- 8.0 mmHg. In multiple linear regression adjusted by smoking and antihypertensive medication showed that clinic systolic BP was the only significant factor related to the ME (beta = -0.44755, p < 0.0001 in male, beta = -0.396, p < 0.0001 in female). Physical activity or job category was not related to ME. CONCLUSIONS: Neither physical activity nor job category is related to ME. This indicates that diagnosis of the masked hypertension is not affected by physical activity or job status.
Blood Pressure ; Blood Pressure Monitoring, Ambulatory ; Energy Metabolism ; Female ; Health Personnel ; Humans ; Hypertension ; Linear Models ; Male ; Masked Hypertension ; Masks ; Motor Activity ; Smoke ; Smoking

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Association of Hypertension and Obesity with Echocardiographic Left Ventricular Hypertrophy or Microalbuminuria in a General Population in South Korea.

Yu Mi KIM ; Sang Woong HAN ; Bae Ken KIM ; Mi Kyung KIM ; Bo Youl CHOI ; Jin Ho SHIN

Journal of the Korean Society of Hypertension.2011;17(4):156-165. doi:10.5646/jksh.2011.17.4.156

BACKGROUND: Both left ventricular hypertrophy (LVH) and microalbuminuria (MA) are well described markers or surrogate for cardiovascular outcome. Many factors are known to be related to the two markers which are encountered together in some patients. But the epidemiological backgrounds for the two markers are not clearly demonstrated so far. METHODS: Measurements of echocardiographic left ventricular mass index (LVMI) and MA were introduced to the population survey in Yangpyeong County, Korea in 2005 and 2006 for 1,767 among 2,028 subjects. The criteria for MA were 17-250 mg/g of albumin creatinine ratio (ACR) in male and 25-355 mg/g in female. 1,636 data were analyzed. RESULTS: Age was 60.9 +/- 10.4 years and the proportion of female was 59.4% (972). Body mass index (BMI) was 24.7 +/- 3.21 kg/m2 and blood pressure were 124.1 +/- 17.3 mm Hg/80.0 +/- 10.5 mm Hg. LVMI was 45.3 +/- 11.6 g/m2.7 and ACR was 23.9 +/- 150.9 mg/g. Prevalence of LVH and MA were 23.5% and 12.2%, respectively. In male/female, odds ratios for MA were 1.035 (range, 1.010-1.061)/1.01 (range, 0.988-1.032) for age, 0.962 (range, 0.882-1.049)/0.941 (range, 0.881-1.006) for BMI, 1.754 (range, 1.097-2.804)/2.158 (range, 1.413-3.298) for hypertension (HTN), 4.87 (range, 2.883-8.226)/2.154 (range, 1.311-3.539) for diabetes, 1.005 (range, 0.999-1.012)/1.007 (range, 1.002-1.012) for cholesterol, and 1.011 (range, 0.987-1.035)/1.011 (range, 0.994-1.029) for LVH. CONCLUSIONS: In a population level, even if diabetes was strongest factor for MA, HTN is also independent factor for MA in both genders.
Albuminuria ; Blood Pressure ; Body Mass Index ; Cholesterol ; Creatinine ; Female ; Humans ; Hypertension ; Hypertrophy ; Hypertrophy, Left Ventricular ; Korea ; Male ; Obesity ; Odds Ratio ; Prevalence ; Republic of Korea

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Current Controversies over the Management of Elderly Hypertension with Impaired Renal Function.

Moon Jae KIM

Journal of the Korean Society of Hypertension.2011;17(4):148-155. doi:10.5646/jksh.2011.17.4.148

Both hypertension and aging impact renal function. Elderly patients are more likely to have chronic kidney disease (CKD), usually defined by estimated glomerular filtration rate 60 mL/min/1.73 m2. Multiple studies over the past two decades have shown that CKD is a powerful cardiovascular disease (CVD) risk factor. Reduced kidney function in elderly people is a marker for adverse outcomes. The major goals of lowering blood pressure (BP) in patients with CKD include reduction of mortality, CVD events and slowing progression. Main considerations in the management of hypertension include selection of a target BP and selection of agents used to attain the chosen target. Current clinical practice guidelines for BP targets and choice of anti-hypertensive agents in elderly patients with CKD are not specific. Older patients with CKD might experience increased mortality and hospitalizations in association with lower baseline BP values. This review outlines controversies in applying current guidelines for the management of BP to older patients with CKD. Because of the high burden of other comorbidities in older patients with CKD, strict adherence to guidelines for the management of hypertension may not always represent the most adequate approach.
Aged ; Aging ; Antihypertensive Agents ; Blood Pressure ; Cardiovascular Diseases ; Comorbidity ; Glomerular Filtration Rate ; Hospitalization ; Humans ; Hypertension ; Kidney ; Renal Insufficiency, Chronic ; Risk Factors

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Cyclophilin A: A Mediator of Cardiovascular Pathology.

Nwe Nwe SOE ; Bradford C BERK

Journal of the Korean Society of Hypertension.2011;17(4):133-147. doi:10.5646/jksh.2011.17.4.133

Cyclophilin A (CyPA) is a 17 kDa, ubiquitously expressed multifunctional protein that possesses peptidylprolyl cis-trans isomerase activity and scaffold function. Its expression is increased in inflammatory conditions including rheumatoid arthritis, autoimmune disease and cancer. Intracellular CyPA regulates protein trafficking, signal transduction, transcription regulation and the activity of certain other proteins. Secreted CyPA activates cardiovascular cells resulting in a variety of cardiovascular diseases; including vascular remodeling, abdominal aortic aneurysms formation, atherosclerosis, cardiac hypertrophy and myocardial ischemic reperfusion injury.
Aortic Aneurysm, Abdominal ; Arthritis, Rheumatoid ; Atherosclerosis ; Autoimmune Diseases ; Cardiomegaly ; Cardiovascular Diseases ; Cyclophilin A ; Cyclophilins ; Myocardial Reperfusion Injury ; Oxidative Stress ; Protein Transport ; Proteins ; Quaternary Ammonium Compounds ; Signal Transduction

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