Cardiovascular Changes During Maturation and Ageing in Male and Female Spontaneously Hypertensive Rats

Chan, Vincent; Fenning, Andrew; Levick, Scott P.; Loch, D. S.; Chunduri, Prasad; Iyer, Abishek; Teo, Yi Ling; Hoey, Andrew; Wilson, Kristin; Burstow, Darryl J.; Brown, Lindsay

doi:10.1097/fjc.0b013e3182102c3b

Cited by 34 publications

(37 citation statements)

References 61 publications

(64 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Further, our observation of significant overlap in protein aggregates between hypertensive and aging hearts suggests that hypertension may in some respects be considered to accelerate or mimic cardiac aging. Physiologically, many functional characteristics of the hypertensive heart mirror those seen with cardiac aging, such as fibrosis and impaired diastolic relaxation (35;36). …”

Section: Discussionmentioning

confidence: 99%

Age- and Hypertension-Associated Protein Aggregates in Mouse Heart Have Similar Proteomic Profiles

et al. 2016

View full text Add to dashboard Cite

Neurodegenerative diseases are largely defined by protein aggregates in affected tissues. Aggregates contain some shared components as well as proteins thought to be specific for each disease. Aggregation has not previously been reported in the normal, aging heart or the hypertensive heart. Detergent-insoluble protein aggregates were isolated from mouse heart and characterized on 2D gels. Their levels increased markedly and significantly with aging and following sustained angiotensin-II-induced hypertension. Of the aggregate components identified by high-resolution proteomics, half changed in abundance with age (392/787) or with sustained hypertension (459/824), while 30% (273/901) changed concordantly in both, each P<0.05. One fifth of these proteins were previously associated with age-progressive neurodegenerative and/or cardiovascular diseases — e.g. ApoE, ApoJ, ApoA-IV, clusterin, complement C3, and others involved in stress-response and protein-homeostasis pathways. Since fibrosis is a characteristic of both aged and hypertensive hearts, we posited that aging of fibroblasts may contribute to the aggregates observed in cardiac tissue. Indeed, as cardiac myofibroblasts “senesced” (approached their replicative limit) in vitro, they accrued aggregates with many of the same constituent proteins observed in vivo during natural aging or sustained hypertension. In summary, we have shown for the first time that compact (detergent-insoluble) protein aggregates accumulate during natural aging, chronic hypertension and in vitro myofibroblast senescence, sharing many common proteins. Thus, aggregates that arise from disparate causes (aging, hypertension, replicative senescence) may have common underlying mechanisms of accrual.

show abstract

Section: Discussionmentioning

confidence: 99%

Age- and Hypertension-Associated Protein Aggregates in Mouse Heart Have Similar Proteomic Profiles

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Findings from studies of changes in the vasculature that accompany aging in human and animal models support the concept that aging is an independent risk factor for cardiovascular disease [14–17]. Salient features of age-associated changes in the vascular system include luminal dilation, intimal and medial thickening, vascular stiffening, and endothelial dysfunction [18].…”

Section: Changes In the Vasculature With Agingmentioning

confidence: 97%

The Role of Oxidative Stress and Inflammation in Cardiovascular Aging

Xia

Kalionis

et al. 2014

BioMed Research International

186

145

View full text Add to dashboard Cite

Age is an independent risk factor of cardiovascular disease, even in the absence of other traditional factors. Emerging evidence in experimental animal and human models has emphasized a central role for two main mechanisms of age-related cardiovascular disease: oxidative stress and inflammation. Excess reactive oxygen species (ROS) and superoxide generated by oxidative stress and low-grade inflammation accompanying aging recapitulate age-related cardiovascular dysfunction, that is, left ventricular hypertrophy, fibrosis, and diastolic dysfunction in the heart as well as endothelial dysfunction, reduced vascular elasticity, and increased vascular stiffness. We describe the signaling involved in these two main mechanisms that include the factors NF-κB, JunD, p66Shc, and Nrf2. Potential therapeutic strategies to improve the cardiovascular function with aging are discussed, with a focus on calorie restriction, SIRT1, and resveratrol.

show abstract

“…96 This sexual dimorphism persists through adulthood; male SHR are more hypertensive than females until after females stop estrus cycling (10–12 months of age), when, by 16 months of age, blood pressure is higher in females than males. 97 Male SHRs also develop signs of heart failure (HF) by 24 months, but female animals do not develop the ventricular stiffness or dilation that is observed in the males. 97 Sexual dimorphisms are also observed at the level of the cardiac myocyte as SHR left ventricular myocyte diastolic and systolic sarcomere dynamics were reduced compared to normotensive controls; this observation was more pronounced in male SHR myocytes.…”

Section: Animal Models Of Cardiovascular Diseasementioning

confidence: 99%

“…97 Male SHRs also develop signs of heart failure (HF) by 24 months, but female animals do not develop the ventricular stiffness or dilation that is observed in the males. 97 Sexual dimorphisms are also observed at the level of the cardiac myocyte as SHR left ventricular myocyte diastolic and systolic sarcomere dynamics were reduced compared to normotensive controls; this observation was more pronounced in male SHR myocytes. 98 The progress of disease and sexual dimorphisms are similar to those observed in men and women, making this model particularly useful.…”

Section: Animal Models Of Cardiovascular Diseasementioning

confidence: 99%

The Importance of Biological Sex and Estrogen in Rodent Models of Cardiovascular Health and Disease

Blenck

Harvey

Reckelhoff

et al. 2016

Circulation Research

161

131

View full text Add to dashboard Cite

Nearly one-third of deaths in the United States are caused by cardiovascular disease (CVD) each year. In the past, CVD was thought to mainly affect men leading to the exclusion of women and female animals from clinical studies and preclinical research. In light of sexual dimorphisms in CVD, a need exists to examine baseline cardiac differences in humans and the animals used to model CVD. In humans, sex differences are apparent at every level of cardiovascular physiology from action potential duration and mitochondrial energetics to cardiac myocyte and whole heart contractile function. Biological sex is an important modifier of the development of CVD with younger women generally being protected, but this cardioprotection is lost later in life, suggesting a role for estrogen. While endogenous estrogen is most likely a mediator of the observed functional differences in both health and disease, the signaling mechanisms involved are complex and are not yet fully understood. To investigate how sex modulates CVD development, animal models are essential tools and should be useful in the development of therapeutics. This review will focus on describing the cardiovascular sexual dimorphisms that exist both physiologically as well as in common animal models of CVD.

show abstract

Cardiovascular Changes During Maturation and Ageing in Male and Female Spontaneously Hypertensive Rats

Abstract: Ageing male SHRs in contrast to the female SHRs, better mimic the chronic heart failure in humans produced by chronic hypertension. Ageing male SHRs could then be used to investigate proposed therapeutic interventions for chronic congestive heart failure in humans.

Cited by 34 publications

References 61 publications

Age- and Hypertension-Associated Protein Aggregates in Mouse Heart Have Similar Proteomic Profiles

Age- and Hypertension-Associated Protein Aggregates in Mouse Heart Have Similar Proteomic Profiles

The Role of Oxidative Stress and Inflammation in Cardiovascular Aging

The Importance of Biological Sex and Estrogen in Rodent Models of Cardiovascular Health and Disease

Contact Info

Product

Resources

About