Fight or flight effects on heart health: new funding

Five biomedical researchers from at Waipapa Taumata Rau University of Auckland have been awarded project grants totalling $834,781 over three years to advance discovery and development of new treatments for diseases that impact communities – and ultimately to save lives. 

One of the Heart Foundation project grants will support Dr Nikki Earle to complete crucial analysis for female and Māori participants in the landmark Multi-Ethnic New Zealand study of Acute Coronary Syndromes (MENZACS). 

The study has been running since 2015 and has enrolled over 2500 New Zealanders who have survived their first heart attack. By using extensive clinical data and biomarkers, including genomics, researchers hope to develop personalised interventions and reduce recurrent events among people with coronary disease.  

Earle says throughout their lifespan, women can experience female-specific risk factors for heart disease, yet these remain largely unrecognised by established risk screening tools. 

“By focusing on women, we aim to better understand how heart attacks differ by sex, and to identify risk markers for subsequent events that are specific to women, such as menopausal status and pregnancy-related disorders.” 

Research fellow in physiology, Carol Bussey, another recipient of the Heart Foundation funding, looks forward to greater data on women’s heart health which will ultimately lead to diagnoses and treatments which are appropriate, effective, and safe for every patient. 

“Cardiovascular disease in women remains under-diagnosed and under-treated, and in up to 69 percent of cases, the first symptom recorded for women is sudden cardiac death,” Bussey says.

“A wide range of cardiovascular diseases that are more common in women have been linked to dysregulation of the sympathetic (fight-or-flight) nervous system. Limited data available suggests women’s hearts and sympathetic nervous system function is different to men’s.” 

Meanwhile, research fellows Drs Audrys Pauza and Dr Igor Simoes Assuncao Felippe are both recipients of three-year Heart Foundation research fellowships exploring different aspects of carotid body activity, the special sensor which monitors oxygen in blood. 

Pauza’s focus is on better understanding the mechanisms which cause the carotid bodies to stay active in disease states, then to explore ways to silence this activity.   

“What’s fascinating is that the carotid body is a multimodal sensor,” he says. “Besides oxygen, it senses a variety of signals in the circulation; in fact, different stimuli acting on the organ trigger different reflex motor responses. Some solely stimulate breathing, others promote sympathetic nerve activity – the latter being harmful and associated with increased cardiovascular risk." 

Pauza says by using state-of-the-art single-cell RNA sequencing and other advanced techniques to study gene expression, we can look at the cellular make-up of the carotid body to identify those linked to harmful nerve activity.  

“This research will not only broaden our understanding of how the body maintains its inner balance, homeostasis, but may also lead to new therapies that target the 'harmful’ cells while preserving the ones making sure we never run out of breath.” 

Aberrant carotid body activity is also linked to an exaggerated sympathetic (fight-or-flight) nervous system activity, a major contributor to hypertension, heart failure and sudden cardiac death. However it is not well controlled by current medications. 

A pre-clinical translational project managed by research fellow Dr Igor Felippe will investigate whether a new class of drugs to block HIF-2α in the carotid body can treat hypertension and improve cardiovascular outcomes in heart failure rates.  

“Importantly,” says Felippe, “HIF-2α inhibitors have been FDA-approved for human use as an adjuvant treatment of kidney cancer.  

“If our results are positive, HIF-2α inhibitors can be rapidly repurposed to treat cardiovascular disease in a first-in-human clinical trial to reduce mortality and improve patients’ quality of life.” 

Cardiac researcher Dr June-Chiew (JC) Han from the Auckland Bioengineering Institute has been awarded one of two prestigious Heart Foundation Senior Fellowships and received a small project grant. His work focuses on cardiac efficiency, looking at the energy of the heart and testing three medications that could help increase heart efficiency and potentially improve and even prevent right-heart failure. 

Project grants awarded

• Dr Igor Simoes Assuncao Felippe (Physiology): Treating cardiovascular disease with HIF-2α inhibitors – $199,319 over three years  
• Dr Audrys Pauza (Physiology): Multimodal chemosensory circuits controlling sympathetic drive in hypertension – $133,818 over three years   
• Dr Carol Bussey (Physiology): Sex differences in sympathetic cardiac regulation – $159,772 over three years   
• Dr Nikki Earle (Medicine): Advancing heart health equity: leveraging biomarker and genomic insights from the Multi-Ethnic New Zealand study of Acute Coronary Syndromes (MENZACS) – $143,954 over two years  
• Dr Nishith Patel (Medical and Health Sciences): Radiomics, biomechanics and aortic dissection – $197,968 over two years