TDT: a highly potent and stable chimeric natriuretic peptide for heart failure treatment S. Vink, Z. Dekan, S. L. Burke, A. Brust, F. Meuris-Vancon, K. J. Poth, G. A. Head, P. F. Alewood Australian Journal of Chemistry, 2026 Natriuretic peptides (NPs) are body fluid volume modulators that have implications in the treatment and management of several conditions, including heart failure, chronic respiratory disease and renal dysfunction. Congestive heart failure is a major burden for the health system; thus, improved therapeutics for the treatment of this condition are highly desired. The natriuretic and diuretic properties of the natriuretic peptides make them ideal candidates for the treatment of congestive heart failure. However, current therapeutics from this family of peptides are far from ideal and suffer from poor pharmacokinetic properties. In the last 20 years, there has been growing interest in NPs from reptilian venom due to high potency and stability. In the present work, Tadendocor (TDT), a chimeric NP, has been produced, which is a combination of the N- and C-terminal tails of taipan natriuretic peptide c (TNPc) from Oxyuranus microlepidotus with the 17-residue intramolecular ring of Dendroaspis natriuretic peptide (DNP) from Dendroaspis angusticeps. This peptide was found to possess increased stability to a range of endopeptidases and proteases and was active at human natriuretic peptide receptor A (hNPR-A) with similar potency to human atrial natriuretic peptide (hANP). Point mutations within the intramolecular ring further increased the potency at hNPR-A, with the H12R, N22G mutant being the most active. Mini-PEGylation with a variety of branched and linear PEG groups did not significantly affect the potency of Nle 29 TDT [H12R/N22G] at hNPR-A, but allowed for oral delivery in vivo. The attachment of a >20-kDa PEG group reduced the potency at hNPR-A by 10-fold but significantly increased the half-life in vivo. This chimeric snake NP represents a promising candidate for the development of a stable, potent NP therapeutic for heart failure.
Annexin-A1 deficiency uncovers female-specific pathways in blood pressure control and cardiovascular remodeling in mice Jaideep Singh, Kristy L. Jackson, Haoyun Fang, Feng Shii Tang, Cindy Gueguen, Alex M. Parker, HsinErh Chen, Cameron J. Nowell, Helen Kiriazis, Ekaterina Salimova, Owen L. Woodman, Rebecca H. Ritchie, Geoffrey A. Head, David W. Greening, Cheng Xue Qin Communications Biology, 2025 Cardiovascular disease exhibits distinct sex-based differences, yet the mechanisms underlying these differences remain under-explored. The pro-resolving mediator annexin-A1 (ANXA1) is a pivotal regulator in inflammation resolution and tissue homeostasis, including within the cardiovascular system. However, the sex-specific differences in ANXA1 in blood pressure regulation have not been investigated. Here, we demonstrate that deficiency of ANXA1 exacerbates angiotensin II-induced adverse aortic and cardiac structural remodeling, mitochondrial proteome dysregulation, and impaired mitochondrial function in preclinical hypertensive models, exacerbated in females. Mechanistically, we demonstrate that estrogen upregulates ANXA1 levels, associated with dysregulation of inflammatory and mitochondrial networks, suggesting that the estrogen-ANXA1 axis plays a critical role in modulating inflammation and preventing pathological remodeling. In conclusion, this study advances the understanding of female-specific cardiac and aortic tissue and cellular alterations in hypertension, providing a platform for developing therapeutic ANXA1 mimetics that address the unique pathophysiological features of hypertension in females. Annexin-A1 shields against hypertension-induced cardiovascular damage, with heightened effects in females. Estrogen-driven upregulation of annexin-A1 unveils a novel, sex-specific protective axis, offering innovative targets for tailored cardiovascular therapies.
Blood pressure measurement at kiosks in public spaces: systematic review and consensus statement by the European Society of Hypertension Working Group on Blood Pressure Monitoring and Cardiovascular Variability endorsed by the International Society of Hypertension and the World Hypertension League George S. Stergiou, Konstantinos G. Kyriakoulis, Anastasios Kollias, Richard J. McManus, Ariadni Menti, Gianfranco Parati, Aletta E. Schutte, Jiguang Wang, Kei Asayama, Roland Asmar, Grzegorz Bilo, Niamh Chapman, Takeshi Fujiwara, Geoffrey Head, Nadia Kahn, Kazuomi Kario, Yan Li, Efstathios Manios, Dimitrios Mariglis, Anastasia S. Mihailidou, Paul Muntner, Martin Myers, Teemu Niiranen, Takayoshi Ohkubo, Stefano Omboni, Athanasios Protogerou, Francesca Saladini, James Sharman, Daichi Shimbo, Alejandro De La Sierra, Paolo Palatini Journal of Hypertension, 2025 Kiosk devices for unsupervised self-measurement of blood pressure (BP) are being used in public spaces and healthcare settings in several countries. This statement by the European Society of Hypertension (ESH) Working Group on BP Monitoring and Cardiovascular Variability provides a review of the published evidence on kiosk BP devices and consensus recommendations for their requirements and clinical use. A systematic literature search identified 54 relevant studies. Kiosk BP measurements appeared to be close to office BP [mean difference systolic 0.2 mmHg (95% confidence intervals −1.3 to 1.8); diastolic −0.4 mmHg (−3.5 to 2.7)], and higher than daytime ambulatory and home BP [mean difference 6.0 mmHg (1.6–10.4)/5.0 (2–8) and 8.1 mmHg (–2.6 to 18.9)/0.2 (−9.6 to 10.0), respectively]. Randomized or observational studies using kiosk BP measurements for hypertension screening or for assessing hypertension control were also included, as well as studies investigating users’ and healthcare professionals’ opinions, acceptability, and perspectives regarding kiosk BP measurements, and validation studies of kiosk BP devices. These studies had considerable heterogeneity in design, setting, methodology, measurement protocol, and sample size. Thus, at present, the clinical utility of kiosk BP measurements is uncertain. This ESH consensus statement acknowledges the potential of kiosk BP measurement as an emerging method for unsupervised self-measurement in the context of opportunistic screening for hypertension in apparently healthy people and the long-term monitoring of people with diagnosed hypertension. Requirements for the design, validation, function, and use of kiosk BP monitors are provided, together with the pending research questions on their optimal implementation in clinical practice.
Faecal metaproteomics analysis reveals a high cardiovascular risk profile across healthy individuals and heart failure patients Chaoran Yang, Leticia Camargo Tavares, Han-Chung Lee, Joel R. Steele, Rosilene V. Ribeiro, Anna L. Beale, Stephanie Yiallourou, Melinda J. Carrington, David M. Kaye, Geoffrey A. Head, Ralf B. Schittenhelm, Francine Z. Marques Gut Microbes, 2025 The gut microbiota is a crucial link between diet and cardiovascular disease (CVD). Using fecal metaproteomics, a method that concurrently captures human gut and microbiome proteins, we determined the crosstalk between gut microbiome, diet, gut health, and CVD. Traditional CVD risk factors (age, BMI, sex, blood pressure) explained < 10% of the proteome variance. However, unsupervised human protein-based clustering analysis revealed two distinct CVD risk clusters (low-risk and high-risk) with different blood pressure (by 9 mmHg) and sex-dependent dietary potassium and fiber intake. In the human proteome, the low-risk group had lower angiotensin-converting enzymes, inflammatory proteins associated with neutrophil extracellular trap formation and auto-immune diseases. In the microbial proteome, the low-risk group had higher expression of phosphate acetyltransferase that produces SCFAs, particularly in fiber-fermenting bacteria. This model identified severity across phenotypes in heart failure patients and long-term risk of cardiovascular events in a large population-based cohort. These findings underscore multifactorial gut-to-host mechanisms that may underlie risk factors for CVD.
Novel formylpeptide receptor 1/2 agonist limits hypertension-induced cardiovascular damage Jaideep Singh, Kristy L Jackson, Haoyun Fang, Audrey Gumanti, Bethany Claridge, Feng Shii Tang, Helen Kiriazis, Ekaterina Salimova, Alex M Parker, Cameron Nowell, Owen L Woodman, David W Greening, Rebecca H Ritchie, Geoffrey A Head, Cheng Xue Qin Cardiovascular Research, 2024 Aims Formylpeptide receptors (FPRs) play a critical role in the regulation of inflammation, an important driver of hypertension-induced end-organ damage. We have previously reported that the biased FPR small-molecule agonist, compound17b (Cmpd17b), is cardioprotective against acute, severe inflammatory insults. Here, we reveal the first compelling evidence of the therapeutic potential of this novel FPR agonist against a longer-term, sustained inflammatory insult, i.e. hypertension-induced end-organ damage. The parallels between the murine and human hypertensive proteome were also investigated. Methods and results The hypertensive response to angiotensin II (Ang II, 0.7 mg/kg/day, s.c.) was attenuated by Cmpd17b (50 mg/kg/day, i.p.). Impairments in cardiac and vascular function assessed via echocardiography were improved by Cmpd17b in hypertensive mice. This functional improvement was accompanied by reduced cardiac and aortic fibrosis and vascular calcification. Cmpd17b also attenuated Ang II-induced increased cardiac mitochondrial complex 2 respiration. Proteomic profiling of cardiac and aortic tissues and cells, using label-free nano-liquid chromatography with high-sensitivity mass spectrometry, detected and quantified ∼6000 proteins. We report hypertension-impacted protein clusters associated with dysregulation of inflammatory, mitochondrial, and calcium responses, as well as modified networks associated with cardiovascular remodelling, contractility, and structural/cytoskeletal organization. Cmpd17b attenuated hypertension-induced dysregulation of multiple proteins in mice, and of these, ∼110 proteins were identified as similarly dysregulated in humans suffering from adverse aortic remodelling and cardiac hypertrophy. Conclusion We have demonstrated, for the first time, that the FPR agonist Cmpd17b powerfully limits hypertension-induced end-organ damage, consistent with proteome networks, supporting development of pro-resolution FPR-based therapeutics for treatment of systemic hypertension complications.
The pro-resolving mediator, annexin A1 regulates blood pressure, and age-associated changes in cardiovascular function and remodeling Jaideep Singh, Kristy L. Jackson, Feng Shii Tang, Ting Fu, Cameron Nowell, Ekaterina Salimova, Helen Kiriazis, Rebecca H. Ritchie, Geoffrey A. Head, Owen L. Woodman, Cheng Xue Qin FASEB Journal, 2024 Aging is associated with chronic, low‐level inflammation which may contribute to cardiovascular pathologies such as hypertension and atherosclerosis. This chronic inflammation may be opposed by endogenous mechanisms to limit inflammation, for example, by the actions of annexin A1 (ANXA1), an endogenous glucocorticoid‐regulated protein that has anti‐inflammatory and pro‐resolving activity. We hypothesized the pro‐resolving mediator ANXA1 protects against age‐induced changes in blood pressure (BP), cardiovascular structure and function, and cardiac senescence. BP was measured monthly in conscious mature (4‐month) and middle‐aged (12‐month) ANXA1‐deficient (ANXA1−/−) and wild‐type C57BL/6 mice. Body composition was measured using EchoMRI, and both cardiac and vascular function using ultrasound imaging. Cardiac hypertrophy, fibrosis and senescence, vascular fibrosis, elastin, and calcification were assessed histologically. Gene expression relevant to structural remodeling, inflammation, and cardiomyocyte senescence were also quantified. In C57BL/6 mice, progression from 4 to 12 months of age did not affect the majority of cardiovascular parameters measured, with the exception of mild cardiac hypertrophy, vascular calcium, and collagen deposition. Interestingly, ANXA1−/− mice exhibited higher BP, regardless of age. Additionally, age progression had a marked impact in ANXA1−/− mice, with markedly augmented vascular remodeling, impaired vascular distensibility, and body composition. Consistent with vascular dysfunction, cardiac dysfunction, and hypertrophy were also evident, together with markers of senescence and inflammation. These findings suggest that endogenous ANXA1 plays a critical role in regulating BP, cardiovascular function, and remodeling and delays cardiac senescence. Our findings support the development of novel ANXA1‐based therapies to prevent age‐related cardiovascular pathologies.
Cardiovascular characterisation of a novel mouse model that combines hypertension and diabetes co-morbidities Arpeeta Sharma, J. Choi, A. Watson, Leila Li, Thomas Sonntag, Man Kit Sam Lee, A. Murphy, M. D. De Blasio, G. Head, R. Ritchie, J. D. de Haan Scientific Reports, 2023 Epidemiologic data suggest that the prevalence of hypertension in patients with diabetes mellitus is ∼1.5-2.0 times greater than in matched non-diabetic patients. This co-existent disease burden exacerbates cardiac and vascular injury, leading to structural and functional changes to the myocardium, impaired cardiac function and heart failure. Oxidative stress and persistent low-grade inflammation underlie both conditions, and are identified as major contributors to pathological cardiac remodelling. There is an urgent need for effective therapies that specifically target oxidative stress and inflammation to protect against cardiac remodelling. Animal models are a valuable tool for testing emerging therapeutics, however, there is a notable lack of appropriate animal models of co-morbid diabetes and hypertension. In this study, we describe a novel preclinical mouse model combining diabetes and hypertension to investigate cardiac and vascular pathology of co-morbid disease. Type 1 diabetes was induced in spontaneously hypertensive, 8-week old, male Schlager (BPH/2) mice via 5 consecutive, daily injections of streptozotocin (55 mg/kg in citrate buffer; i.p.). Non-diabetic mice received citrate buffer only. After 10 weeks of diabetes induction, cardiac function was assessed by echocardiography prior to post-mortem evaluation of cardiomyocyte hypertrophy, interstitial fibrosis and inflammation by histology, RT-PCR and flow cytometry. We focussed on the oxidative and inflammatory stress pathways that contribute to cardiovascular remodelling. In particular, we demonstrate that markers of inflammation (monocyte chemoattractant protein; MCP-1), oxidative stress (urinary 8-isoprostanes) and fibrosis (connective tissue growth factor; CTGF) are significantly increased, whilst diastolic dysfunction, as indicated by prolonged isovolumic relaxation time (IVRT), is elevated in this diabetic and hypertensive mouse model. In summary, this pre-clinical mouse model provides researchers with a tool to test therapeutic strategies unique to co-morbid diabetes and hypertension, thereby facilitating the emergence of novel therapeutics to combat the cardiovascular consequences of these debilitating co-morbidities.
Requirements for design and function of blood pressure measuring devices used for the management of hypertension: Consensus Statement by the European Society of Hypertension Working Group on Blood Pressure Monitoring and Cardiovascular Variability and STRIDE BP George S. Stergiou, Gianfranco Parati, Anastasios Kollias, Aletta E. Schutte, Kei Asayama, Roland Asmar, Grzegorz Bilo, Alejandro de la Sierra, Eamon Dolan, Jan Filipovsky, Geoffrey Head, Kazuomi Kario, Konstantinos G. Kyriakoulis, Giuseppe Mancia, Efstathios Manios, Ariadni Menti, Richard J. McManus, Anastasia S. Mihailidou, Paul Muntner, Teemu Niiranen, Takayoshi Ohkubo, Stefano Omboni, Athanasios Protogerou, Francesca Saladini, James Sharman, Andrew Shennan, Daichi Shimbo, Jirar Topouchian, Jiguang Wang, Eoin O’Brien, Paolo Palatini Journal of Hypertension, 2023 Objective: To develop scientific consensus recommendations for the optimal design and functions of different types of blood pressure (BP) measuring devices used in clinical practice for the detection, management, and long-term follow-up of hypertension. Methods: A scientific consensus meeting was performed by the European Society of Hypertension (ESH) Working Group on BP Monitoring and Cardiovascular Variability and STRIDE BP (Science and Technology for Regional Innovation and Development in Europe) during the 2022 Scientific Meeting of the ESH in Athens, Greece. Manufacturers were also invited to provide their feedback on BP device design and development. Thirty-one international experts in clinical hypertension and BP monitoring contributed to the development of consensus recommendations on the optimal design of BP devices. Statement: International consensus was reached on the requirements for the design and features of five types of BP monitors, including office (or clinic) BP monitors, ambulatory BP monitors, home BP monitors, home BP telemonitors, and kiosk BP monitors for public spaces. For each device type “essential” requirements (must have), and “optional” ones (may have) are presented, as well as additional comments on the optimal device design and features. Conclusions: These consensus recommendations aim at providing manufacturers of BP devices with the requirements that are considered mandatory, or optional, by clinical experts involved in the detection and management of hypertension. They are also directed to administrative healthcare personnel involved in the provision and purchase of BP devices so that they can recommend the most appropriate ones.
Blood pressure variability: methodological aspects, clinical relevance and practical indications for management - a European Society of Hypertension position paper ∗ Gianfranco Parati, Grzegorz Bilo, Anastasios Kollias, Martino Pengo, Juan Eugenio Ochoa, Paolo Castiglioni, George S. Stergiou, Giuseppe Mancia, Kei Asayama, Roland Asmar, Alberto Avolio, Enrico G. Caiani, Alejandro De La Sierra, Eamon Dolan, Andrea Grillo, Przemysław Guzik, Satoshi Hoshide, Geoffrey A. Head, Yutaka Imai, Eeva Juhanoja, Thomas Kahan, Kazuomi Kario, Vasilios Kotsis, Reinhold Kreutz, Konstantinos G. Kyriakoulis, Yan Li, Efstathios Manios, Anastasia S. Mihailidou, Pietro Amedeo Modesti, Stefano Omboni, Paolo Palatini, Alexandre Persu, Athanasios D. Protogerou, Francesca Saladini, Paolo Salvi, Pantelis Sarafidis, Camilla Torlasco, Franco Veglio, Charalambos Vlachopoulos, Yuqing Zhang Journal of Hypertension, 2023
Rodent models of hypertension Hamdi A. Jama, Rikeish R. Muralitharan, Chudan Xu, Joanne A. O'Donnell, Mariane Bertagnolli, Bradley R. S. Broughton, Geoffrey A. Head, Francine Z. Marques British Journal of Pharmacology, 2022
Home blood pressure monitoring: Methodology, clinical relevance and practical application: A 2021 position paper by the Working Group on Blood Pressure Monitoring and Cardiovascular Variability of the European Society of Hypertension Gianfranco Parati, George S. Stergiou, Grzegorz Bilo, Anastasios Kollias, Martino Pengo, Juan Eugenio Ochoa, Rajiv Agarwal, Kei Asayama, Roland Asmar, Michel Burnier, Alejandro De La Sierra, Cristina Giannattasio, Philippe Gosse, Geoffrey Head, Satoshi Hoshide, Yutaka Imai, Kazuomi Kario, Yan Li, Efstathios Manios, Jonathan Mant, Richard J. McManus, Thomas Mengden, Anastasia S. Mihailidou, Paul Muntner, Martin Myers, Teemu Niiranen, Angeliki Ntineri, Eoin O’Brien, José Andres Octavio, Takayoshi Ohkubo, Stefano Omboni, Paul Padfield, Paolo Palatini, Dario Pellegrini, Nicolas Postel-Vinay, Agustin J. Ramirez, James E. Sharman, Andrew Shennan, Egle Silva, Jirar Topouchian, Camilla Torlasco, Ji Guang Wang, Michael A. Weber, Paul K. Whelton, William B. White, Giuseppe Mancia Journal of Hypertension, 2021
Differential sympathetic response to lesion-induced chronic kidney disease in rabbits Yusuke Sata, Sandra L. Burke, Anna M.D. Watson, Jay C. Jha, Cindy Gueguen, Nina Eikelis, Kyungjoon Lim, Kristy L. Jackson, Gavin W. Lambert, Karin A.M. Jandeleit-Dahm, Kate M. Denton, Murray D. Esler, Markus P. Schlaich, Geoffrey A. Head Kidney International, 2020
Renal nerves contribute to hypertension in Schlager BPH/2J mice Cindy Gueguen, Kristy L. Jackson, Francine Z. Marques, Nina Eikelis, Sarah Phillips, Emily R. Stevenson, Fadi J. Charchar, Gavin W. Lambert, Pamela J. Davern, Geoffrey A. Head Hypertension Research, 2019
Chronic sympathetic driven hypertension promotes atherosclerosis by enhancing hematopoiesis Annas Al-Sharea, Man K. S. Lee, Alexandra Whillas, Danielle L. Michell, Waled A. Shihata, Alyce J. Nicholls, Olivia D. Cooney, Michael J. Kraakman, Camilla Bertuzzo Veiga, Ann-Maree Jefferis, Kristy Jackson, Prabhakara R. Nagareddy, Gavin Lambert, Connie H. Y. Wong, Karen L. Andrews, Geoff A. Head, Jaye Chin-Dusting, Andrew J. Murphy Haematologica, 2019
Health-related quality of life and blood pressure 12months after renal denervation Gavin W. Lambert, Dagmara Hering, Petra Marusic, Alicia Thorp, Yusuke Sata, Rebecca Lee, Jacqueline Duval, Louise Hammond, Geoffrey A. Head, Murray D. Esler, Elisabeth A. Lambert, John B. Dixon, Arup K. Dhar, David A. Barton, Markus P. Schlaich Journal of Hypertension, 2015
European society of hypertension practice guidelines for ambulatory blood pressure monitoring Gianfranco Parati, George Stergiou, Eoin O’Brien, Roland Asmar, Lawrence Beilin, Grzegorz Bilo, Denis Clement, Alejandro de la Sierra, Peter de Leeuw, Eamon Dolan, Robert Fagard, John Graves, Geoffrey A. Head, Yutaka Imai, Kazuomi Kario, Empar Lurbe, Jean-Michel Mallion, Giuseppe Mancia, Thomas Mengden, Martin Myers, Gbenga Ogedegbe, Takayoshi Ohkubo, Stefano Omboni, Paolo Palatini, Josep Redon, Luis M. Ruilope, Andrew Shennan, Jan A. Staessen, Gert vanMontfrans, Paolo Verdecchia, Bernard Waeber, Jiguang Wang, Alberto Zanchetti, Yuqing Zhang Journal of Hypertension, 2014
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European society of hypertension position paper on ambulatory blood pressure monitoring Eoin O’Brien, Gianfranco Parati, George Stergiou, Roland Asmar, Laurie Beilin, Grzegorz Bilo, Denis Clement, Alejandro de la Sierra, Peter de Leeuw, Eamon Dolan, Robert Fagard, John Graves, Geoffrey A. Head, Yutaka Imai, Kazuomi Kario, Empar Lurbe, Jean-Michel Mallion, Giuseppe Mancia, Thomas Mengden, Martin Myers, Gbenga Ogedegbe, Takayoshi Ohkubo, Stefano Omboni, Paolo Palatini, Josep Redon, Luis M. Ruilope, Andrew Shennan, Jan A. Staessen, Gert vanMontfrans, Paolo Verdecchia, Bernard Waeber, Jiguang Wang, Alberto Zanchetti, Yuqing Zhang Journal of Hypertension, 2013
Developmental origins of obesity-related hypertension Sarah L Henry, Benjamin Barzel, Ryan J Wood‐Bradley, Sandra L Burke, Geoffrey A Head, James A Armitage Clinical and Experimental Pharmacology and Physiology, 2012
Reduced phosphoinositide 3-kinase (p110α) activation increases the susceptibility to atrial fibrillation Lynette Pretorius, Xiao-Jun Du, Elizabeth A. Woodcock, Helen Kiriazis, Ruby C.Y. Lin, Silvana Marasco, Robert L. Medcalf, Ziqiu Ming, Geoffrey A. Head, Joon Win Tan, Nelly Cemerlang, Junichi Sadoshima, Tetsuo Shioi, Seigo Izumo, Elena V. Lukoshkova, Anthony M. Dart, Garry L. Jennings, Julie R. McMullen American Journal of Pathology, 2009
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