The cardiovascular system is an essential component of mammalian biology. It is a complex network of various tissues and structures with unique functions. The function of the cardiovascular system is to supply nutrients including oxygen to the various cells, tissues and organs within the body, and remove waste products from them. Given the importance of this role, it is not surprising that there are countless regulatory mechanisms at the molecular, cellular and tissue levels that are required to support this functional system. Perturbations in parts of this system are likely to lead to abnormalities, and thus give rise to cardiovascular-related diseases. Despite the currently expanding list of genes reported to be involved in a variety of cardiovascular-related diseases, including calcific aortic valve disease (CAVD), the functions and associated pathways of these factors in both normal and pathological physiology have yet to be fully understood, such as at the transcriptomic level. In this thesis, a genome-wide transcriptomic atlas of the healthy mammalian cardiovascular system was generated using the sheep as a large animal model. This atlas was generated using RNA-seq, with the aim of further understanding normal gene expression patterns in the context of the known physiology of healthy mammalian tissues. Through this work, I identified novel gene networks and detailed functional clustering of co-expressed genes with region-specific expression and specialised cardiovascular roles. One interesting cluster was highly expressed in the cardiac valves, and shared genes found in physiological bone development, such as bone morphogenetic protein 4 (BMP4), collagen type I alpha 2 (COL1A2), Sry homeobox 8 (SOX8) and bone gamma-carboxyglutamate protein (BGLAP), some of which have been implicated in vascular calcification. Further to this work, I studied the expression profiles of these key cardiovascular genes during development in the sheep from foetal to adult stages. In addition, I investigated the gene expression patterns of various key vascular calcification genes. These studies showed differential expression of genes in the different cardiovascular tissues, demonstrating transcriptional differences between these different tissues known to have different functions. CAVD involves progressive valve leaflet thickening and severe calcification, resulting in impaired leaflet motion. The in vitro calcification of primary rat, human, porcine and bovine aortic valve interstitial cells (VICs) is commonly employed to examine the mechanisms of CAVD. However, to date, no published studies have utilised cell lines to investigate this process Thus, in this project, I generated and evaluated the calcification potential of an immortalised cell line derived from sheep aortic VICs (SAVICs). This novel large animal in vitro model of CAVD was demonstrated to calcify under high calcium and phosphate conditions. Changes in the expression of key calcification genes during VIC calcification was also observed, including increased mRNA expression of bone markers Runt-related transcription factor 2 (RUNX2) and sodium-dependent phosphate transporter 1 (PiT1), and a concomitant decrease in matrix Gla protein (MGP) mRNA expression. In addition, the role of extracellular nucleotides and their receptors (P2 receptors), which have been previously shown to be important in bone and vascular calcification, were investigated using SAVICs in vitro. This study has shown that extracellular nucleotides, particularly adenosine 5’-triphosphate (ATP) and uridine 5’-triphosphate (UTP) and other agonists of P2 receptors, reduced VIC calcification in vitro. Moreover, the cutting-edge gene-editing technology, clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein-9 nuclease (Cas9), was successfully applied to generate large animal models of cardiovascular-related diseases. In this project, I applied the CRISPR/Cas9 technology to edit ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) and fibrillin 1 (FBN1) to generate two models of vascular calcification and Marfan Syndrome (MFS), respectively. In the ENPP1-edited animals, soft tissue calcification has been observed in the biallelic mutant and homozygous pigs. In this project, I have developed a range of novel in vitro and in vivo tools to advance the study of cardiovascular disease. These studies demonstrate that large animal models are highly valuable in the field of cardiovascular biology. The in vivo and in vitro experimental models described should facilitate detailed analysis of cardiovascular molecular biology and ultimately lead to therapies which will minimise the morbidity and mortality currently arising from cardiovascular pathology.

Orientador: Jacqueline Costa Teixeira Caramori / Banca: João Egídio Romão / Banca: Luís Cuadrado Martin / Banca: Pasqual Barretti / Banca: Rodrigo Bueno de Oliveira / Resumo: A doença cardiovascular é a principal causa de mortalidade nos pacientes com doença renal crônica (DRC) em programa de hemodiálise e a calcificação vascular (CV) é comum nesta população. O principal objetivo deste estudo foi avaliar a associação de marcadores do metabolismo mineral e ósseo com a presença e progressão da CV em uma coorte de pacientes em diálise; secundariamente, objetivou identificar as associações clínicas, laboratoriais e da composição corporal sobre a presença e progressão da CV. Foram incluídos maiores de 18 anos em diálise crônica há mais de 90 dias. Os pacientes foram submetidos à biópsia óssea no início do seguimento e analisados dados de histomorfometria. Para investigar CV foi utilizada a somatória dos índices radiológicos de Kauppila e Adragão em dois momentos, no início, coincidindo com a realização da biópsia óssea e após 12 meses. Além da investigação para CV foram realizadas avaliações clínicas, hormonais, inflamatórias, bioquímicas e nutricionais. Resultados: 60 pacientes completaram o estudo, 41,7 % do sexo feminino, 43,4% diabéticos, média de idade de 56 anos, variação de 25 a 89 anos. No seguimento, 75% dos pacientes apresentavam CV e a progressão ocorreu em 56,86%. Na análise multivariada, a idade > 60 anos (Odds ratio=50.2, 95%CI= 4.1-618,4, p=0.002), FGF23 > 3000 Ru/ml (Odds ratio=5.7, 95%IC= 1,00-329, p=0.05), e fetuína A >673 μ/l (Odds ratio=7.34, 95%CI= 1,26-43,7, p=0.03) estiveram associados com a CV. Para progressão da CV, a associação foi mostrada para idade > 60 anos (Odds ratio=4.3, 95%CI= 1.003-18.5, p=0.049), fetuína A >673 μ/l (Odds ratio=6.4, 95%CI= 1.47-27.9, p=0.01), e o não uso de estatinas (Odds ratio=5.6, 95%CI= 1.13-28.1, p=0.03). Não foi possível mostrar associações com os marcadores da remodelação óssea ou com os parâmetros achados de histomorfometria tanto no diagnostico como na progressão da CV. Conclusão: O presente... / Abstract: Cardiovascular disease is the main cause of death in patients with chronic kidney disease (CKD) in hemodialysis and vascular calcification (VC) is common in this population. The main objective of this study was to evaluate the association of markers of mineral and disorder on the presence and progression of VC in a cohort of dialysis patients. Secondarily, it was intended to identify associations between clinical, laboratory and body composition markers with the presence and progression of VC. There were included patients aged over 18 years on chronic dialysis for more than 90 days. The patients were submitted to bone biopsy at the beginning of the follow-up and histomorphometric data analyzed. To investigate VC a sum of radiological scores of Kauppila and Adragão were obtained in two occasions: at the beginning of the follow-up and after 12 months. In addition, clinical, hormonal, inflammatory, biochemical and nutritional evaluation were performed. Results: Sixty patients completed the study; 41.7% were female, 43.4% diabetics, and the average age was 56.7 years (range 25 to 89 years). At the beginning of the follow-up, 75% of the patients showed VC and its progression was observed in 56.8%. At multivariate analysis, age > 60 years (Odds ratio = 50.2, 95% CI=4.1-618.4, p=0.002), FGF23>3000 Ru/mL (Odds ratio = 5.7, 95% CI=1.00-329, p=0.05), and fetuin A>673 g/l (Odds ratio = 7.34, 95% CI=1.26-43.7, p=0.03) were associated with VC. As for the VC progression, the association was shown to age>60 years old (Odds ratio = 4.3, 95% CI=1.003-18.5, p=0.049), fetuin A> 673 g/l (Odds ratio = 6.4, 95% CI = 1.47-27.9, p=0.01), and the non-use of statins (Odds ratio = 5.6, 95% CI=1.13-28.1, p=0.03). It was not possible to show the association with bone turnover markers and the histomorphometric findings both in diagnosis and progression of VC. In conclusion, the present study reinforces the role of aging, the FGF23 level and the statin protection in ... / Doutor

PET imaging, using the bone tracer Na18F, allows the non-invasive location of atherosclerotic plaques that are at risk of rupture. However, the spatial resolution of PET is only 4-5 mm, limiting the mechanistic information this technique can provide. In this thesis, the use of fluorescence and Raman imaging to elucidate the mechanism of micro-calcification within atherosclerotic plaques has been investigated. A number of fluorescent probes to detect fluoride and calcium have been synthesised. One of the fluoride probes has been shown to be selective for fluoride however, the concentration of fluoride required to activate the probe is order of magnitudes higher than the amount of Na18F used for PET imaging making it problematic to use for future studies. On the other hand, a calcium probe has been shown to: selectively bind to hydroxyapatite (HAP); permit visualisation and quantification of HAP in both vascular and bone cell models; and effectively stain cultured aortic sections and whole mouse aorta for OPT imaging. Building on these preliminary data, fluorescence imaging and immunohistochemistry (IHC) imaging of both healthy and atherosclerotic tissue that were previously subjected to PET imaging, were successfully carried out showing the ability of the probe to detect HAP in human vascular tissue. IHC staining for Osteoprotegerin (OPG) and Osteopontin (OPN), two bone proteins recently detected in vascular tissue, showed the co-localization of OPG with the probe. Conversely, the OPN was shown to localize in areas surrounding high OPG and probe signal. To determine the exact composition of vascular calcification, Raman spectroscopy was also used. It is believed that the biosynthetic pathway to HAP passes through a series of transitional states; each of these has different structural characteristics which can be studied using Raman spectroscopy. In particular, HAP has a strong characteristic Raman peak at 960 cm-1. An increase in HAP concentration has been detected by Raman in both calcified cell models and aortic sections. When human vascular tissue was analysed, an additional peak at 973 cm-1 was present suggesting the presence of whitlockite (WTK) in this tissue as well as HAP.

O objetivo deste trabalho foi avaliar a associação de calcificação da aorta abdominal (CAA) com marcadores do metabolismo ósseo: densidade mineral óssea (DMO), dados laboratoriais (cálcio, fósforo, 25OH-vitamina D, PTH) e clínicos em uma população brasileira de idosos. Este foi um estudo de corte transversal onde foram incluídos 815 indivíduos com idade igual ou superior a 65 anos. Os dados demográficos e de estilo de vida, bem como os parâmetros clínicos que identificam os fatores de risco para osteoporose e calcificação vascular foram obtidos por um questionário padronizado. Densidade mineral óssea (DMO) e parâmetros laboratoriais foram avaliados em todos os indivíduos. Foram realizadas radiografias de coluna lombar para a análise de calcificação da aorta abdominal nos segmentos correspondentes às vértebras L1 a L4. Para cada segmento lombar foi dada uma pontuação de 0-3 para as paredes anterior e posterior, com um escore máximo de 24 pontos (Kaupilla et al., 1997). Resultados: 63,2% dos idosos apresentavam algum grau de CAA, com um escore médio de 4,68 5,88. Analisando as variáveis contínuas observamos que o escore de CAA foi correlacionado diretamente à idade, fósforo sérico, LDL-colesterol (LDL-C), triglicérides e inversamente ao índice de massa corpórea (IMC), DMO do colo do fêmur e DMO do fêmur total (p<0,05). Em relação às variáveis binárias o escore de CAA foi associado à história de fraturas prévias por fragilidade, baixa atividade física, quedas no último ano, tabagismo atual e hipertensão arterial (p<0,05). A análise de regressão linear múltipla demonstrou que o escore de CAA foi diretamente relacionado à idade (p<0,001), tabagismo atual (p<0,001), hipertensão arterial (p=0,002), LDL-C (p=0,05), triglicérides (p=0,002), fósforo sérico (p=0,005) e inversamente associado à DMO de fêmur total (p<0,001). Um aumento no escore de CAA foi observado com a elevação dos níveis séricos de fósforo [ 2,4mg/dL: escore de CAA = 1,9 (DP: 3,9); 2,5-3,5mg/dL: escore de CAA = 4,5 (DP: 5,6) e > 3,5mg/dL : escore de CAA = 5,3 (SD: 6,3) p=0,003]. Este estudo demonstrou que, além dos fatores de risco clássicos para doença cardiovascular (HAS, tabagismo e lípides), o fósforo sérico e a DMO do fêmur total foram fatores de risco adicionais ao complexo processo de calcificação vascular em idosos da comunidade / The aim of this study was to analyze abdominal aortic calcification (AAC) and its possible association with bone mineral density (BMD) as well as the clinical and laboratory data. This was a cross-sectional study conducted between 2005 to 2007, with a population-based sample of older men and women living in Brazil. Eight hundred and fifteen subjects 65 years old were studied. The risk factors for osteoporosis and cardiovascular disease, demographic data and lifestyle characteristics were collected using a standardized questionnaire. BMD was measured by DXA. Kauppilas method was used to quantify the AAC score (AACS) by spine X-rays. Laboratory analyses were also performed. AAC was observed in 63.2% of subjects with a mean AACS of 4.68 (5.88). AACS was directly correlated with age, phosphorus, LDL-cholesterol, triglycerides, and inversely correlated with body mass index, femoral neck BMD and total femur BMD (p<0.05). Regarding binary variables, the AACS was associated with previous fragility fractures, current smoking, low physical activity, falls and arterial hypertension (p<0.05). Multiple linear regression analysis demonstrated that the AACS was positively associated with age (p<0.001), current smoking (p<0.001), arterial hypertension (p=0.002), LDL-C (p=0.05), triglycerides (p=0.002), phosphate (p=0.005) and negatively associated with total femur BMD (p<0.001). An increased of AACS was observed with the elevation of serum phosphorus levels [ 2.4mg/dL: AACS=1.9 (SD:3.9); 2.5-3.5mg/dL: AACS=4.5 (SD:5.6) and > 3.5mg/dL: AACS=5.3 (SD:6.3), p=0.003]. Our study identified serum phosphate and hip BMD as additional players in the complex process of vascular calcification outside the setting of kidney failure in community-dwelling older population and extended the previous observations of well-known risk factors for cardiovascular disease

O objetivo deste trabalho foi avaliar a associação de calcificação da aorta abdominal (CAA) com marcadores do metabolismo ósseo: densidade mineral óssea (DMO), dados laboratoriais (cálcio, fósforo, 25OH-vitamina D, PTH) e clínicos em uma população brasileira de idosos. Este foi um estudo de corte transversal onde foram incluídos 815 indivíduos com idade igual ou superior a 65 anos. Os dados demográficos e de estilo de vida, bem como os parâmetros clínicos que identificam os fatores de risco para osteoporose e calcificação vascular foram obtidos por um questionário padronizado. Densidade mineral óssea (DMO) e parâmetros laboratoriais foram avaliados em todos os indivíduos. Foram realizadas radiografias de coluna lombar para a análise de calcificação da aorta abdominal nos segmentos correspondentes às vértebras L1 a L4. Para cada segmento lombar foi dada uma pontuação de 0-3 para as paredes anterior e posterior, com um escore máximo de 24 pontos (Kaupilla et al., 1997). Resultados: 63,2% dos idosos apresentavam algum grau de CAA, com um escore médio de 4,68 5,88. Analisando as variáveis contínuas observamos que o escore de CAA foi correlacionado diretamente à idade, fósforo sérico, LDL-colesterol (LDL-C), triglicérides e inversamente ao índice de massa corpórea (IMC), DMO do colo do fêmur e DMO do fêmur total (p<0,05). Em relação às variáveis binárias o escore de CAA foi associado à história de fraturas prévias por fragilidade, baixa atividade física, quedas no último ano, tabagismo atual e hipertensão arterial (p<0,05). A análise de regressão linear múltipla demonstrou que o escore de CAA foi diretamente relacionado à idade (p<0,001), tabagismo atual (p<0,001), hipertensão arterial (p=0,002), LDL-C (p=0,05), triglicérides (p=0,002), fósforo sérico (p=0,005) e inversamente associado à DMO de fêmur total (p<0,001). Um aumento no escore de CAA foi observado com a elevação dos níveis séricos de fósforo [ 2,4mg/dL: escore de CAA = 1,9 (DP: 3,9); 2,5-3,5mg/dL: escore de CAA = 4,5 (DP: 5,6) e > 3,5mg/dL : escore de CAA = 5,3 (SD: 6,3) p=0,003]. Este estudo demonstrou que, além dos fatores de risco clássicos para doença cardiovascular (HAS, tabagismo e lípides), o fósforo sérico e a DMO do fêmur total foram fatores de risco adicionais ao complexo processo de calcificação vascular em idosos da comunidade / The aim of this study was to analyze abdominal aortic calcification (AAC) and its possible association with bone mineral density (BMD) as well as the clinical and laboratory data. This was a cross-sectional study conducted between 2005 to 2007, with a population-based sample of older men and women living in Brazil. Eight hundred and fifteen subjects 65 years old were studied. The risk factors for osteoporosis and cardiovascular disease, demographic data and lifestyle characteristics were collected using a standardized questionnaire. BMD was measured by DXA. Kauppilas method was used to quantify the AAC score (AACS) by spine X-rays. Laboratory analyses were also performed. AAC was observed in 63.2% of subjects with a mean AACS of 4.68 (5.88). AACS was directly correlated with age, phosphorus, LDL-cholesterol, triglycerides, and inversely correlated with body mass index, femoral neck BMD and total femur BMD (p<0.05). Regarding binary variables, the AACS was associated with previous fragility fractures, current smoking, low physical activity, falls and arterial hypertension (p<0.05). Multiple linear regression analysis demonstrated that the AACS was positively associated with age (p<0.001), current smoking (p<0.001), arterial hypertension (p=0.002), LDL-C (p=0.05), triglycerides (p=0.002), phosphate (p=0.005) and negatively associated with total femur BMD (p<0.001). An increased of AACS was observed with the elevation of serum phosphorus levels [ 2.4mg/dL: AACS=1.9 (SD:3.9); 2.5-3.5mg/dL: AACS=4.5 (SD:5.6) and > 3.5mg/dL: AACS=5.3 (SD:6.3), p=0.003]. Our study identified serum phosphate and hip BMD as additional players in the complex process of vascular calcification outside the setting of kidney failure in community-dwelling older population and extended the previous observations of well-known risk factors for cardiovascular disease

Made available in DSpace on 2016-08-12T18:48:44Z (GMT). No. of bitstreams: 0 Previous issue date: 2015-06-21. Added 1 bitstream(s) on 2016-08-12T18:50:58Z : No. of bitstreams: 1 000865115.pdf: 1167817 bytes, checksum: d666ddace602ebad1f4085e5014c5972 (MD5) / A doença cardiovascular é a principal causa de mortalidade nos pacientes com doença renal crônica (DRC) em programa de hemodiálise e a calcificação vascular (CV) é comum nesta população. O principal objetivo deste estudo foi avaliar a associação de marcadores do metabolismo mineral e ósseo com a presença e progressão da CV em uma coorte de pacientes em diálise; secundariamente, objetivou identificar as associações clínicas, laboratoriais e da composição corporal sobre a presença e progressão da CV. Foram incluídos maiores de 18 anos em diálise crônica há mais de 90 dias. Os pacientes foram submetidos à biópsia óssea no início do seguimento e analisados dados de histomorfometria. Para investigar CV foi utilizada a somatória dos índices radiológicos de Kauppila e Adragão em dois momentos, no início, coincidindo com a realização da biópsia óssea e após 12 meses. Além da investigação para CV foram realizadas avaliações clínicas, hormonais, inflamatórias, bioquímicas e nutricionais. Resultados: 60 pacientes completaram o estudo, 41,7 % do sexo feminino, 43,4% diabéticos, média de idade de 56 anos, variação de 25 a 89 anos. No seguimento, 75% dos pacientes apresentavam CV e a progressão ocorreu em 56,86%. Na análise multivariada, a idade > 60 anos (Odds ratio=50.2, 95%CI= 4.1-618,4, p=0.002), FGF23 > 3000 Ru/ml (Odds ratio=5.7, 95%IC= 1,00-329, p=0.05), e fetuína A >673 μ/l (Odds ratio=7.34, 95%CI= 1,26-43,7, p=0.03) estiveram associados com a CV. Para progressão da CV, a associação foi mostrada para idade > 60 anos (Odds ratio=4.3, 95%CI= 1.003-18.5, p=0.049), fetuína A >673 μ/l (Odds ratio=6.4, 95%CI= 1.47-27.9, p=0.01), e o não uso de estatinas (Odds ratio=5.6, 95%CI= 1.13-28.1, p=0.03). Não foi possível mostrar associações com os marcadores da remodelação óssea ou com os parâmetros achados de histomorfometria tanto no diagnostico como na progressão da CV. Conclusão: O presente... / Cardiovascular disease is the main cause of death in patients with chronic kidney disease (CKD) in hemodialysis and vascular calcification (VC) is common in this population. The main objective of this study was to evaluate the association of markers of mineral and disorder on the presence and progression of VC in a cohort of dialysis patients. Secondarily, it was intended to identify associations between clinical, laboratory and body composition markers with the presence and progression of VC. There were included patients aged over 18 years on chronic dialysis for more than 90 days. The patients were submitted to bone biopsy at the beginning of the follow-up and histomorphometric data analyzed. To investigate VC a sum of radiological scores of Kauppila and Adragão were obtained in two occasions: at the beginning of the follow-up and after 12 months. In addition, clinical, hormonal, inflammatory, biochemical and nutritional evaluation were performed. Results: Sixty patients completed the study; 41.7% were female, 43.4% diabetics, and the average age was 56.7 years (range 25 to 89 years). At the beginning of the follow-up, 75% of the patients showed VC and its progression was observed in 56.8%. At multivariate analysis, age > 60 years (Odds ratio = 50.2, 95% CI=4.1-618.4, p=0.002), FGF23>3000 Ru/mL (Odds ratio = 5.7, 95% CI=1.00-329, p=0.05), and fetuin A>673 g/l (Odds ratio = 7.34, 95% CI=1.26-43.7, p=0.03) were associated with VC. As for the VC progression, the association was shown to age>60 years old (Odds ratio = 4.3, 95% CI=1.003-18.5, p=0.049), fetuin A> 673 g/l (Odds ratio = 6.4, 95% CI = 1.47-27.9, p=0.01), and the non-use of statins (Odds ratio = 5.6, 95% CI=1.13-28.1, p=0.03). It was not possible to show the association with bone turnover markers and the histomorphometric findings both in diagnosis and progression of VC. In conclusion, the present study reinforces the role of aging, the FGF23 level and the statin protection in ...

BACKGROUND Vascular calcification is a major risk factor for cardiovascular morbidity and mortality in patients with end stage renal disease (ESRD). In Western countries, Blacks with ESRD appear to have lesser degrees of vascular calcification compared to non-Blacks. However, there is no published data on the association of ethnic differences in vascular calcification and survival in ESRD from Sub-Saharan Africa. METHODS This study assessed the 5-year change in vascular calcification and mortality in a previously published cohort of patients with ESRD. Vascular calcification was assessed by abdominal aortic calcification score (lateral abdominal radiograph) and vascular stiffness by pulse wave velocity. RESULTS Sixty-six of the original 74 participants, studied a baseline, were identified. The median age was 46.6 years (37.6-59.2) and 57.6% were women. Abdominal aortic calcification showed no progression among Blacks [baseline range 0-5, follow up range 0-8 (p=1.00)], but a nonsignificant trend to progression among non-Blacks [baseline range 0-19, follow up range 0-22 (p=0.066)]. Black participants did not display a survival advantage (p=0.870). Overall, sepsis was the most common cause of mortality (64% of those with an identifiable cause of death). Non-Blacks had higher parathyroidectomy rates than Blacks with 9/30 cases compared to 2/36 (p=0.036). After adjustment for parathyroidectomy at follow up, the odds ratio of having abdominal vascular calcification score of ≥1 amongst non-Blacks was 8.6-fold greater compared to Blacks (p= 0.03). Central aortic systolic pressures (CASP) and pulse wave velocities (PWV) were higher in the study population than age matched normative values. At follow up, a positive correlation (r=0.3) was observed between PWV and abdominal aortic calcification (p=0.04). Elevated baseline coronary artery calcification score and FGF-23 level at baseline were not associated with a difference in mortality. CONCLUSION There was no significant progression in vascular calcification among Blacks. After adjusting for increased parathyroidectomy rates, there was a greater progression of vascular calcification amongst non-Blacks compared to Blacks highlighting possible ethnic differences in calcium phosphate metabolism in patients with ESRD. The lack of vascular calcification progression in Blacks was not however associated with improved survival, but the sample size was small.

京都大学 / 0048 / 新制・課程博士 / 博士(医科学) / 甲第21029号 / 医科博第90号 / 新制||医科||6(附属図書館) / 京都大学大学院医学研究科医科学専攻 / (主査)教授 山下 潤, 教授 湊谷 謙司, 教授 原田 浩 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

No description available.

Cardiovascular disease is the leading cause of non-communicable disease in the whole world killing 17 million people in 2012. Among the many vascular diseases is vascular calcification (VC) which is the mineral build up in the walls of blood vessels. Medial calcification is the plaque buildup in the medial layer of the blood vesicle that is characterized by arterial stiffness and high blood pressure. Current calcification research involves two dimensional (2D) lab methods such as flat petri dishes to investigate the mechanism that causes and inhibits vascular calcification. Research has shown that the use of three-dimensional (3D) models can be beneficial in mimicking the in vitro environment of the human body for lab practices. We aim to create a 3D benchtop model for vascular calcification research from decellularized carotid porcine arteries to understand the more accurate mechanisms that lead to the plaque buildup in the medial layer of the artery wall.