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8 results on '"Blythe, Hazel C."'

2. Investigating the link between sympathetic nerve activation and inflammation in the progression of hypertensive heart disease

Author

Blythe, Hazel C., Nightingale, Angus, Hart, Emma, Suleiman, Saadeh, and Abdala Sheikh, Ana Paula

Abstract

Hypertension is the leading modifiable cause of premature death worldwide. Some hypertensive individuals develop left ventricular (LV) hypertrophy (LVH) and myocardial fibrosis, increasing cardiovascular morbidity and mortality, whereas some hypertensive individuals have normal LV structure and function. The sympathetic nervous system (SNS) and immune system are known to play a role in hypertension and cardiac remodelling; however, it remains unknown whether inflammation causes sympathetic overactivation, or if elevated sympathetic nerve activity (SNA) induces inflammation in hypertension. This thesis hypothesised that inflammation would precede sympathetic overactivation in the development of cardiac remodelling. Temporal changes in lumbar SNA and inflammatory markers in spontaneously hypertensive rats (SHRs) were observed from 10-weeks-old to 15-weeks-old, with circulating IL-18 found to be a significant predictor of LVH. However, due to issues with data collection, lumbar SNA data was inconclusive. This thesis also aimed to identify whether resting SNA or SNA reactivity was associated with cardiac remodelling in humans. Resting SNA was found to predict concentric cardiac remodelling, and SNA reactivity was a predictor of cardiac fibrosis in people with and without hypertension. Resting SNA was also found to predict circulating IL-18, confirming a link between SNA and inflammation, although no inflammatory markers were associated with cardiac remodelling. However, a type III collagen synthesis marker, amino-terminal propeptide of procollagen type III (PIIINP) was found to predict LVH, but no markers predicted myocardial fibrosis. Additionally, stress induced increases in SNA were found to be sustained in recovery in hypertensive but not normotensive individuals, having implications for increased cardiovascular risk. Finally, hypertensive individuals had an increased rise in pro-inflammatory markers following exercise, with change in IL-10 being an independent predictor of ECV. Overall, this thesis has shown resting SNA and SNA reactivity predict cardiac remodelling and circulating IL-18, IL-10 and PIIINP may be potential biomarkers to predict cardiac remodelling.

Published
2023

5. Investigating the link between sympathetic nerve activation and inflammation in the progression of hypertensive heart disease

Author

Blythe, Hazel C and Blythe, Hazel C

Abstract

Hypertension is the leading modifiable cause of premature death worldwide. Some hypertensive individuals develop left ventricular (LV) hypertrophy (LVH) and myocardial fibrosis, increasing cardiovascular morbidity and mortality, whereas some hypertensive individuals have normal LV structure and function. The sympathetic nervous system (SNS) and immune system are known to play a role in hypertension and cardiac remodelling; however, it remains unknown whether inflammation causes sympathetic overactivation, or if elevated sympathetic nerve activity (SNA) induces inflammation in hypertension. This thesis hypothesised that inflammation would precede sympathetic overactivation in the development of cardiac remodelling. Temporal changes in lumbar SNA and inflammatory markers in spontaneously hypertensive rats (SHRs) were observed from 10-weeks-old to 15-weeks-old, with circulating IL-18 found to be a significant predictor of LVH. However, due to issues with data collection, lumbar SNA data was inconclusive. This thesis also aimed to identify whether resting SNA or SNA reactivity was associated with cardiac remodelling in humans. Resting SNA was found to predict concentric cardiac remodelling, and SNA reactivity was a predictor of cardiac fibrosis in people with and without hypertension. Resting SNA was also found to predict circulating IL-18, confirming a link between SNA and inflammation, although no inflammatory markers were associated with cardiac remodelling. However, a type III collagen synthesis marker, amino-terminal propeptide of procollagen type III (PIIINP) was found to predict LVH, but no markers predicted myocardial fibrosis. Additionally, stress induced increases in SNA were found to be sustained in recovery in hypertensive but not normotensive individuals, having implications for increased cardiovascular risk. Finally, hypertensive individuals had an increased rise in pro-inflammatory markers following exercise, with change in IL-10 being an independent pred

Published
2023

7. Aneurysm severity is suppressed by deletion of CCN4:CCN4 in aneurysms

Author

Williams, Helen, Wadey, Kerry S, Frankow, Aleksandra, Blythe, Hazel C, Forbes, Tessa, Johnson, Jason L, and George, Sarah J

Subjects
CCN-4, WISP1, WISP-1, cardiovascular system, aneurysm, Wnt pathway, atherosclerosis
Abstract

Patients with abdominal aortic aneurysms are frequently treated with high-risk surgery. A pharmaceutical treatment to reverse aneurysm progression could prevent the need for surgery and save both lives and healthcare resources. Since CCN4 regulates cell migration, proliferation and apoptosis, processes involved in aneurysm progression, it is a potential regulator of aneurysm progression.We investigated the role of CCN4 in a mouse aneurysm model, using apolipoprotein-E knockout (ApoE-/-) mice fed high fat diet and infused with Angiotensin II (AngII). Blood pressure was similarly elevated in CCN4-/-ApoE-/- mice and CCN4+/+ApoE-/- mice (controls) in response to AngII infusion. Deletion of CCN4 significantly reduced the number of ruptured aortae, both thoracic and abdominal aortic area, and aneurysm grade score, compared to controls. Additionally, the frequency of vessel wall remodelling and the number of elastic lamina breaks was significantly suppressed in CCN4-/-ApoE-/- mice compared to controls. Immunohistochemistry revealed a significantly lower proportion of macrophages, while the proportion of smooth muscle cells was not affected by the deletion of CCN4. There was also a reduction in both proliferation and apoptosis in CCN4-/-ApoE-/- mice compared to controls. In vitro studies showed that CCN4 significantly increased monocyte adhesion beyond that seen with TNF and stimulated macrophage migration by more than 3-fold.In summary, absence of CCN4 reduced aneurysm severity and improved aortic integrity, which may be the result of reduced macrophage infiltration and cell apoptosis. Inhibition of CCN4 could offer a potential therapeutic approach for the treatment of aneurysms.

Published
2021

8. Aging in females is associated with changes in respiratory modulation of sympathetic nerve activity and blood pressure.

Author

Adams ZH, Blythe HC, Charkoudian N, Curry TB, Joyner MJ, Kendrick AH, Nightingale AK, Abdala Sheikh AP, and Hart EC

Subjects
Adult, Female, Male, Humans, Blood Pressure, Respiratory Rate, Respiration, Autonomic Nervous System, Aging, Hypertension, Hypotension
Abstract

Sympathetic nerve activity (SNA) is tightly coupled with the respiratory cycle. In healthy human males, respiratory modulation of SNA does not change with age. However, it is unclear how this modulation is affected by age in females. We investigated whether respiratory sympathetic modulation is altered in healthy postmenopausal (PMF) versus premenopausal female (YF), and younger male (YM) adults, and determined its relationship to resting blood pressure. Muscle SNA (MSNA; microneurography), respiration (transducer belt), ECG, and continuous blood pressure were measured in 12 YF, 13 PMF, and 12 YM healthy volunteers. Respiratory modulation of MSNA was quantified during two phases of the respiratory cycle: mid-late expiration and inspiration/postinspiration. All groups showed respiratory modulation of MSNA ( P < 0.0005). There was an interaction between the respiratory phase and group for MSNA [bursts/100 heartbeats (HB) ( P = 0.004) and bursts/min ( P = 0.029)], with smaller reductions in MSNA during inspiration observed in PMF versus the other groups. Respiratory modulation of blood pressure was also reduced in PMF versus YF (6 [2] vs. 12 [9] mmHg, P = 0.008) and YM (13 [13] mmHg, P = 0.001, median [interquartile range]). The magnitude of respiratory sympathetic modulation was related to resting blood pressure in PMF only, such that individuals with less modulation had greater resting blood pressure. The data indicate that aging in postmenopausal females is associated with less inspiratory inhibition of MSNA. This correlated with a higher resting blood pressure in PMF only. Thus, the reduced modulation of MSNA could contribute to the age-related rise in blood pressure that occurs in females. NEW & NOTEWORTHY The current study demonstrates that respiratory modulation of sympathetic nerve activity (SNA) is reduced in healthy postmenopausal (PMF) versus premenopausal females (YF). Furthermore, respiratory sympathetic modulation was negatively related to resting blood pressure in postmenopausal females, such that blood pressure was greater in individual with less modulation. Reduced respiratory sympathetic modulation may have implications for the autonomic control of blood pressure in aging postmenopausal females, by contributing to age-related sympathetic activation and reducing acute, respiratory-linked blood pressure variation.

Published
2023
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