• 한국발생생물학회지:발생과생식
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• 제17권1호
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• pp.17-24
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• 2013

This study examined the expression of inhibitor of DNA-binding (Id) proteins and vascular endothelial growth factor (VEGF) in the ovary according to female age using a mice model as the first step in investigating the potential role of Ids and VEGF in ovarian aging. C57BL inbred female mice of three age groups (6-9, 14-16, and 23-26 weeks) were injected with 5 IU pregnant mare's serum gonadotropin (PMSG) in order to synchronize the estrus cycle. After 48 h, ovarian expression of Ids and VEGF was analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR), western blot and immunohistochemistry. Ovarian apoptosis was examined by ovarian expression of Bcl-2 and Bcl-xL. Expression of Id-1 and VEGF was decreased with advancing female age, but not Id-2, Id-3, and Id-4. In particular, their expressions were significantly decreased in aged mice of 23-26 weeks compared with the young mice of 6-9 weeks (p < 0.05). In contrast, ovarian apoptosis was greatly increased in the aged mice compared to the young mice. This result suggests that Id-1 may have an implicated role in ovarian aging by associating with VEGF.

• 한국전문물리치료학회지
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• 제5권1호
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• pp.63-78
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• 1998

The decrease of muscle power and muscle size between twenties and seventies was about 30% and 40% respectively. The loss of muscle mass by aging resulted in the decrease of muscle power. The loss of muscle mass was due to the decrease of number of Type I fiber and Type II fiber and size of each muscle fiber. The aging skeletal muscle didn't show the loss of glycolysis capacity but showed 20% decrease of the oxidative enzymes and muscle vascularization. The vigorous endurance exercise training with graded intensity played a role in the vascular proliferation, increase of activity of oxidative enzymes and improvement of $VO_2$ max. The graded resistance exercise also played a role in the muscle hypertrophy and increase of muscle power, if it performed with adequate intensity and period. The exercise adaptation of aging skeletal muscle prevented it from sarcopenia, provided the activity of daily living with great effect and provided the aging related disease, that is Type II diabetes mellitus, arteriosclerosis, hypertension, osteoporosis and obesity, with great effect.

• 대한기계학회논문집A
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• 제32권5호
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• pp.444-450
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• 2008

The conventional studies of the aging effect on cardio-vascular system are mostly obtained from human experiences and can only provide local information. In this study, the effect of fatigue fracture of arterial wall on the blood pressure was investigated by hemodynamic analysis. The aging process was simulated with three stages. The pulse wave velocity increased with age. The systolic blood pressure increases consistently but diastolic blood pressure decreases with age. The simulated results show in good accordance with the clinical ones.

• 전자공학회논문지SC
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• 제44권4호통권316호
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• pp.15-20
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• 2007

현재, 우리나라 당뇨병의 유병률은 빠른 속도로 증가하고 있으며 당뇨병의 유병기간이 길수록 각종 합병증이 발생하여 더욱 심각한 증상을 나타내는데, 그 중 비만 및 고혈당, 당대사장애로 인한 당뇨병성 혈관합병증과 말초 혈관 경화증이 많이 발병하고 있는 실정이다. 따라서 본 연구에서는 광혈류량 측정법(Photoplethysmography)으로 손가락 및 발가락에서 얻어진 맥파의 2차 미분분석을 통해 연령이 비슷한 정상인 50명과 당뇨병으로 확진된 50명의 말초 혈관 탄성도를 객관적으로 비교하고자 하였다. PPG 파형의 2차 미분 분석에 사용되는 평가 인자는 a, b, c, d, e 이고, b/a는 혈관의 탄성도를 의미하며 탄성도가 떨어질수록 b/a의 절대 값은 감소하게 된다. 정상인 50명의 PPG 2차 미분 b/a값은 $-1.09{\pm}0.14$, 당뇨병 환자 50명의 PPG 2차 미분 b/a값은 $-0.81{\pm}0.09$로 정상인에 비해 당뇨병 환장의 말초혈관 탄성도가 감소하였으며, Independent t-test 검정 결과 통계적으로 유의한 차이를 보였다(p<0.05). 본 연구에서는 PPG 파형의 2차 미분 분석을 통하여 정상인과 혈관합병증 발병율이 높은 당뇨병 환자의 말초혈관 탄성도를 비교하였으며, 향후 비침습적이고 간단한 방법으로 당뇨병 환자의 말초혈관 탄성도와 혈관 경화정도를 객관적으로 평가하고 진단함으로써 당뇨병 환자들의 심혈관계질환 사전예방과 치료효과 판정에 도움을 줄 것으로 기대한다.

• Journal of Ginseng Research
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• 제37권1호
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• pp.64-73
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• 2013

Korean red ginseng water extract (KG-WE) has known beneficial effects on the cardiovascular system via inducting nitric oxide (NO) production in endothelium. Endothelial arginase inhibits the activity of endothelial nitric oxide synthase (eNOS) by substrate depletion, thereby reducing NO bioavailability and contributing to vascular diseases including hypertension, aging, and atherosclerosis. In the present study, we demonstrate that KG-WE inhibits arginase activity and negatively regulates NO production and reactive oxygen species generation in endothelium. This is associated with increased dimerization of eNOS without affecting the protein expression levels of either arginase or eNOS. In a vascular tension assay, when aortas isolated from wild type mice were incubated with KG-WE, NO-dependent enhanced vasorelaxation was observed. Furthermore, KG-WE administered via by drinking water to atherogenic model mice being fed high cholesterol diet improved impaired vascular function. Taken together, these results suggest that KG-WE may exert vasoprotective effects through augmentation of NO signaling by inhibiting arginase. Therefore, KG-WE may be useful in the treatment of vascular diseases derived from endothelial dysfunction, such as atherosclerosis.

• Biomolecules & Therapeutics
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• 제31권6호
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• pp.629-639
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• 2023

Cardiovascular diseases (CVDs) are the most common cardiovascular system disorders. Cellular senescence is a key mechanism associated with dysfunction of aged vascular endothelium. Hyaluronic acid and proteoglycan link protein 1 (HAPLN1) has been known to non-covalently link hyaluronic acid (HA) and proteoglycans (PGs), and forms and stabilizes HAPLN1-containing aggregates as a major component of extracellular matrix. Our previous study showed that serum levels of HAPLN1 decrease with aging. Here, we found that the HAPLN1 gene expression was reduced in senescent human umbilical vein endothelial cells (HUVECs). Moreover, a recombinant human HAPLN1 (rhHAPLN1) decreased the activity of senescence-associated β-gal and inhibited the production of senescence-associated secretory phenotypes, including IL-1β, CCL2, and IL-6. rhHAPLN1 also downregulated IL-17A levels, which is known to play a key role in vascular endothelial senescence. In addition, rhHAPLN1 protected senescent HUVECs from oxidative stress by reducing cellular reactive oxygen species levels, thus promoting the function and survival of HUVECs and leading to cellular proliferation, migration, and angiogenesis. We also found that rhHAPLN1 not only increases the sirtuin 1 (SIRT1) levels, but also reduces the cellular senescence markers levels, such as p53, p21, and p16. Taken together, our data indicate that rhHAPLN1 delays or inhibits the endothelial senescence induced by various aging factors, such as replicative, IL-17A, and oxidative stress-induced senescence, thus suggesting that rhHAPLN1 may be a promising therapeutic for CVD and atherosclerosis.

• 대한한의진단학회지
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• 제12권1호
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• pp.42-62
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• 2008

연구배경과 목적: 지첨용적맥파는 광학기술을 이용하여 손가락 끝에서 혈액용적의 변화를 측정하여 맥파를 검출하는 기술로서, 지첨용적맥파에 대한 시간영역 파형분석을 통해 혈관의 노화정도를 파악할 수 있음은 이미 잘 알려진 사실이다. 이에 본 연구자는 시간영역 파형분석을 통해 혈관노화지표를 얻을 수 있다면, 주파수영역분석법을 통해서도 혈관노화지표를 얻을 수 있을 것으로 가정하였다. 본 연구에서는 주파수영역에서 혈관노화지표를 찾기 위해 건강한 성인들을 대상으로 지첨용적맥파를 측정하고 주파수영역에서 분석하여 고조파가 혈관노화 지표로서 활용될 수 있는가 여부를 결정하고자 한다. 연구방법: 건강인 390명(남자 174명과 여자 216명)을 대상으로 안정 후 앙와위에서 30초 동안 지첨용적맥파를 검출하였다. 검출한 맥파신호에서 기저선이 비교적 안정된 5-6개의 맥파주기를 선택하여 시간영역 파형분석을 통해 얻어지는 혈관노화지표인 승각시간, 경화지수, 반사지수, 가속도맥파를 구하였다. 주파수영역분석을 위해서는 빠른 퓨리에변환(FFT)를 실시하여 고조파 성분을 추출하였다. 특정점 검출을 위해서는 AcqKnowledge software의 peak detector 기능을 이용하였다. 연구결과: 표준화된 고조파 파워는 연령증가에 따라 유의하게 감소하였다; nPWR2 (r=-0.286, p<0.0001), nPWR3 (r=-0.482, p<0.0001), nPWR4 (r=-0.564, p<0.0001), nPWRS (r=-0.467, p<0.0001) 및 nPWR6 (r=-0.263, p<0.0001). 표준화된 고조파 파워의 logarithmic scale에서 연령증가에 따라 보다 강한 선형적인 감소가 나타났다; Ln(nPWR2) (r=-0.281, p<0.0001), Ln(nPWR3) (r=-0.492, P<0.0001), Ln(nPWR4) (r=-0.621, P<0.0001), Ln(nPWRS) (r=-0.487, P<0.0001) 및 Ln(nPWR6) (r=-0.273, P<0.0001). 승각시간, 반사지수, 경화지수를 독립변수로 한 중회귀분석에서 Ln(nPWR2) (R-squared=0.451), Ln(nPWR3) (R-squared=0.471) 및 Ln(nPWR4) (R-squared=0.432)는 비교적 잘 설명되었으나, Ln(nPWRS) (R-squared=0.232) 및 Ln(nPWR6) (R-squared=0.183)는 비교적 잘 설명되지 않았다. 결론: 건강인의 지첨용적맥파에서 기준 주파수로 표준화한 고조파 파워는 연령증가에 따라 감소였으며, 주파수영역분석이 가지는 특성을 고려해 볼 때 표준화된 고조파 파워는 기존의 시간영역 파형분석을 통해 얻어지는 혈관노화지표에 비해 잡음에 의한 오차가 보다 적을 것으로 기대된다. 따라서 우리는 표준화된 고조파 파워가 간편하고 용이하게 혈관노화를 반영하는 새로운 지표로서 활용될 수 있을 것으로 생각된다.

• The Korean Journal of Physiology and Pharmacology
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• 제18권2호
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• pp.95-101
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• 2014

Cardiovascular disease is the prime cause of morbidity and mortality and the population ages that may contribute to increase in the occurrence of cardiovascular disease. Arginase upregulation is associated with impaired endothelial function in aged vascular system and thus may contribute to cardiovascular disease. According to recent research, Korean Red Ginseng water extract (KRGE) may reduce cardiovascular disease risk by improving vascular system health. The purpose of this study was to examine mechanisms contributing to age-related vascular endothelial dysfunction and to determine whether KRGE improves these functions in aged mice. Young ($10{\pm}3$ weeks) and aged ($55{\pm}5$ weeks) male mice (C57BL/6J) were orally administered 0, 10, or 20 mg/mouse/day of KRGE for 4 weeks. Animals were sacrificed and the aortas were removed. Endothelial arginase activity, nitric oxide (NO) generation and reactive oxygen species (ROS) production, endothelial nitric oxide synthase (eNOS) coupling, vascular tension, and plasma peroxynitrite production were measured. KRGE attenuated arginase activity, restored nitric oxide (NO) generation, reduced ROS production, and enhanced eNOS coupling in aged mice. KRGE also improved vascular tension in aged vessels, as indicated by increased acetylcholine-induced vasorelaxation and improved phenylephrine-stimulated vasoconstriction. Furthermore, KRGE prevented plasma peroxynitrite formation in aged mice, indicating reduced lipid peroxidation. These results suggest KRGE exerts vasoprotective effects by inhibiting arginase activity and augmenting NO signaling and may be a useful treatment for age-dependent vascular diseases.

• IMMUNE NETWORK
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• 제9권3호
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• pp.106-113
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• 2009

Background: We previously demonstrated remarkable differences in the expression of IL-8/CXCL8 in aortic tissues and vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) compared to VSMC from normotensive Wistar-Kyoto rats (WKY). In the present study, we investigated the direct effect of IL-8/CXCL8 on expression of 12-lipoxygenase (LO), a hypertensive modulator, in SHR VSMC. Methods: Cultured aortic VSMC from SHR and WKY were used. Expression of 12-LO mRNA was determined by real-time polymerase chain reaction. Phosphorlyation of ERK1/2 and production of 12-LO and angiotensin II subtype 1 ($AT_1$) receptor were assessed by Western blots. IL-8/CXCL8-stimulated DNA synthesis was determined by measuring incorporation of [$^3H$]-thymidine. And effect of IL-8/CXCL8 on vascular tone was determined by phenylephrine-induced contraction of thoracic aortic rings. Results: Treatment with IL-8/CXCL8 greatly increased 12-LO mRNA expression and protein production compared to treatment with angiotensin II. IL-8/CXCL8 also increased the expression of the $AT_1$ receptor. The increase in 12-LO induced by IL-8/CXCL8 was inhibited by treatment with an $AT_1$ receptor antagonist. The induction of 12-LO mRNA production and the proliferation of SHR VSMC by IL-8/CXCL8 was mediated by the ERK pathway. The proliferation of SHR VSMC and the vascular contraction in the thoracic aortic ring, both of which were induced by IL-8/CXCL8, were inhibited by baicalein, a 12-LO inhibitor. Conclusion: These results suggest that the potential role of IL-8/CXCL8 in hypertensive processes is likely mediated through the 12-LO pathway.

• 대한영상의학회지
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• 제83권3호
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• pp.527-537
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• 2022

철은 중추신경계 및 인체에 필수적인 성분으로 노화 및 다양한 퇴행성 뇌질환에서 뇌의 철 침착이 증가된다. 철은 MRI에서 독특한 특성을 가지고 있어 인체의 철 침착과 분포를 비침 습적으로 평가 및 정량화가 가능하다. 이 종설에서는 철 영상을 위한 MRI 기법에 대하여 알아보고, 노화 및 알츠하이머병을 포함한 퇴행성 뇌질환에서 변화를 고찰해 보고자 한다. 또한 현재 접근법의 제한점과 앞으로 기대되는 새로운 접근도 확인해 보고자 한다.