Healthy People's Cardiovascular Ageing In North Area Of China And Vascular Ageing's Gene Differential Expression Study

Introduction and ObjectiveIn 20 century, the world has been entering an Irreversible aged societ. Populationaging is a rigorous Challenge to all international society and a strategy to affect acountry's economic and political long-term development. In 1999, China has entered anaged society. The aged population in China will increase by 3 percent per year and willreach 300 million in 2020. From 1990 to 2020, heart diseases are expected to increase120 percent for women and 137 percent for men in developing countries includingChina and India, while only increasing 30 to 60 percent in the developed world.Age has been to be the major risk factor. Cardiovascular aging is defined as aninevitable and inescapable process that originates from progressive decrement ofviability and increment of vulnerability of cardiovascular system with the passage oftime. In this view, cardiovascular aging become "partners" with pathophysiologicaldisease mechanisms to determine the threshold, severity, and prognosis ofcardiovascular disease in older persons.The highlight scientific theme of this 2006's WCC/ESC congress was"cardiovascular diseases and aging". As for the theme of 2006 world heart day, it alsowas "How Young is Your Heart?", the same theme with that of 2006's WCC/ESC.Clearly, the study on the cardiovasdular ageing will be the future academic highlightsand hotspots.On the current WCC/ESC congress, Fuster, President of the World Heart Federation, pointed out"The world's health systems will be severely stretched as rapidly ageingpopulations cause a corresponding increase in the number of cardiovascular diseases.However demographic trends don't have to be cardiologic destiny. We can address theworld population's aging, and the corresponding threat to health care systems, before itbecomes an emergency".In this study, through large sample cross-section survey, 70 items were measuredthose were essential for maintianing a functional cardiovascular system, cardiovascularageing biomarkers were selected and cardiovascular age score CAS were calculatedbased on the biomarkers. Those will contribute some to the china's treatment andprevention of cardiovascular ageing. The aim of first part of population study was toquantitatively assess the progress of healthy people's cardiovascular aging bynon-invasive ways, and analyze the law of cardiovascular aging in the north area ofChina.According to the light thrown by the population study, the ageing—associatedstructural and functional changes of aorta and the law of aortic ageing—relatedremodeling in healthy rats during natural aging were studied and gene fishing diffentialdisplay technology was used to investigate ageing—related remodeling genes, whichwill did much to illustrating possible gene regulation mechanism of vascular ageing—related remodeling and presenting latent gene targets for anti-cardiovascular ageing.MethodsPart 1 population study1. Subject: 855 healthy people from 3 cities Shenyang, Dalian,and Beijing dividedinto 4 groups according to the age,≤44 years old,45～59 years old,60～74 yearsold,≥75 years old.2. Testing items: Total 70 items including blood pressure, heart and carotidultrasonograph, biochemistry, blood routine, urine routine and microinflammationwere measured. 3. Data processing: To observe these items changes with advancing age. And thencardiovascular aging biomarkers were screened out, cardiovascular aging assessmentequation was constructed and Cardiovascular Aging Score (CAS) was calculated.Part 2 animal study1. Grouping: According to the age, 40 healthy male Wistar rats were divided into 4groups, 4, 10, 16 and 22 months group, with 10 rats each group.2. Analysis on the micro-structure and macro-structure of aorta was made for eachgroup rats.3. Differential display: Gene Fishing differential display was used to screen outremodeling related gene.4. RT-PCR: Reverse Transcription-Polymerase Chain Reaction, RT-PCR, was usedto measure mRNA expression level of remodeling related gene.5. Western blot: Western blot was used to measure protein level of remodelingrelated gene.6. Multiple regression: Multiple Regression analysis was used to analysize therelation between gene expression and aorta ageing related remodeling.ResultsPart 1 population study7 items including pulse pressure(PP), carotid artery intimal-medial thickness(IMT),carotid artery end-diastolic velocity(EDV), mitral valve anulus anterior wall A(MVAA),mitral valve anulus lateral wall E(MVLE), fibrinogen(FIB), total cholesterol(TC) wereindependent of Chronological Age (CA) and could be the cardiovascular agingbiomarkers. Meanwhile, CAS was positively correlated with CA (r=0.85, P＜0.05) withthe most rapid change rat in the group of 45～59.Part 2 animal studyWith a slow startup, a obvious speedup and a following speed-down, the vascularageing—related remodeling is not a constant velocity process. The phasic expression of Cacnal c,p22-phox,SDF-1αwas consistent with vascular ageing—related remodelingclosely.Conclusion1. IMT,EDV,PP,MVLE,MVAA,TC,FIB were independent on CA, andwould be the cardiovascular ageing biomarkers.2. CAS can be as the objective index to quantitatively assess cardiovascularaging.3. And with a acceleration of cardiovascular aging rate after 45 years old, thehealthy people's cardiovascular aging is not constant velocity progress and 45 years oldis the key threshold for cardiovascular aging.4. The phasic expression of Cacnalc,p22-phox,SDF-1αmay be the inherentgene regulation mechanism for vascular ageing—related remodeling.5. Cacnalc,p22-phox,SDF-1αseem to be the key genes for startup, speedup andkeeping up of vascular ageing—related remodeling.