Dr Glenn Rodrigo

Lecturer in cardiovascular sciences

B.Sc. (Biological Sciences), University of Leicester, 1980
Ph.D. (Physiology), University of Leicester, 1984

Tel: 0116 258 3023

Email: gcr4@le.ac.uk

Address: Department of Cardiovascular Sciences, University of Leicester, Clinical Sciences Wing, Glenfield General Hospital, Leicester, LE3 9QP

For general enquiries please email the secretary, Louise Goddard, or telephone 0116 256 3405

Research Interests

My laboratory is interested in ischaemia/reperfusion injury in the heart and how the cardioprotective technique of remote ischaemic conditioning works to both protect the heart against I/R injury but also prevent adverse remodelling of the myocardium following ischemic injury. We are also interested in translating this research into positive clinical outcomes for patients with coronary artery disease. We are also interested in the cellular mechanisms responsible for the circadian variations in the cardiovascular system and how this relates to disease conditions. In particular how these circadian rhythms might result in a time-of-day variation in the efficacy of current cardiovascular drugs.

Cardioprotection against Ischaemia/Reperfusion injury of the myocardium and its subsequent remodelling

Remote ischaemic conditioning and prevention of acute reperfusion injury

The application of a transient ischaemic event to an arm results in the production of a signal that travels to the heart in the blood, where the activation of receptors results in a biochemical change to the heart cells rendering them resistant to injury resulting from an acute myocardial infarction (AMI) "heart attack".

Remote Ischaemic conditioning prevents ischaemia/reperfusion injury in isolated adult ventricular cardiomyocytes (fig. 1)
A. Control cells subject to I/R injury showing green viable cells (calcein) and red nuclei of dead cells (PI). B. Cells conditioned with rIC serum from a healthy volunteer prior to I/R. C. Cells conditioned with rIC serum from a Type-2 diabetic patient prior to I/R.
We are interested in this process termed “remote ischaemic conditioning” and how it is influenced by comorbidities often associated with cardiovascular disease, such as diabetes and age. We have shown that serum collected from healthy volunteers subject to remote ischaemic conditioning is able to protect adult ventricular cardiomyocytes against ischaemia/reperfusion injury but that this protection is absent in patients with type 1 or 2 diabetes (Edroos, Vanezis et al. 2012) (see figure 1).

Remote ischaemic conditioning and chronic remodelling process

Modern methods for unblocking the blood vessels of the heart during a heart attack have increased the survivability of an AMI considerably. However, many patients still suffer considerable injury to the muscle of the heart and this can lead to hypertrophic heart disease, heart failure and arrhythmias.

Remote Ischaemic conditioning prevents the endothelin-induced hypertrophic response in H9c2 cardiomyoblasts (fig. 2)
A. Control cells stained for actin with phalloidin-FITC (green) and nuclear stain Hoechst 33342 (blue). B. Cells treated with a hypertrophic stimulus (Endothelin-1). C. Cells conditioned with rIC serum from a healthy volunteer prior to treatment with Endothelin-1
We are currently looking at the ability of remote ischaemic conditioning (rIC) to prevent or reduce the adverse remodelling process that results following injury to the myocardium during an AMI. We have found that serum collected from healthy volunteers subject to remote ischaemic conditioning is able to block the hypertrophic response of cultured cardiac cells to endothelin-1 (Vanezis, Edroos et al. 2012; Vanezis, Butt et al. 2014) (see figure 2).

The cellular basis for the circadian rhythms in the cardiovascular system

Autonomic control of cardiac electrical and mechanical activity

The autonomic nervous system exhibits a profound 24 hour circadian rhythm and is thought to have significant influence on cardiac function and on the development of patho-physiological conditions, both mechanical and electrical.

We have recently shown that sympathetic control of contraction exhibits strong time-of-day variation and this reflects changes in NOS-signalling and Ca2+-regulation (Collins and Rodrigo 2010). Furthermore, this time-of-day variation is absent in spontaneously hypertensive rats with marked left ventricular hypertrophy (Collins, Turrell et al. 2013).

Autonomic control of vascular smooth muscle contraction and its impact on blood pressure

The influence of circadian rhythms on the cardiovascular system is manifest by a nocturnal "dip" in blood pressure associated with a paradoxical increase in total peripheral resistance, which occurs at time-of-day, when the vascular response to vasoconstrictor compounds is heightened, and to vasodilators reduced.

We have recently shown that the time-of-day variation in contraction of resistance vessels to 1-adrenoreceptor activation and vasodilation to acetylcholine reflects circadian variation in eNOS activity (Denniff, Turrell et al. 2013) 

Research Degree Supervision

  • The ability remote ischaemic conditioning (rIC) alter the adverse remodelling of the ventricles following a myocardial infarct. 
    a) Impact on myocardial hypertrophy and fibrosis 
    b) Influence on electrical remodelling and Ca2+-homeostasis mechanisms
  • Is remote ischaemic conditioning (rIC) a viable alternative to exercise as a method to prevent type-2 diabetes in pre-diabetic patients?
  • The role of nitric oxide signalling in the circadian variation of the cardiovascular system
    a) Impact on β-adrenergic signalling in the heart
    b) Influence on endothelial regulation of vascular resistance

Membership of Learned Societies

The Physiological Society of the UK 1987-
The European Working Group on Cardiac Cellular Electrophysiology 1988-

Key Publications

Vanezis AP, Butt M, et al. (2014). 23 The Role of AMPK and PKC{varepsilon} in the Attenuation of ET-1 Induced Cardiomyocyte Hypertrophy by RIC Human Serum. Heart 100 Suppl 1: A8-9.

Collins HE, Turrell HE, et al. (2013). Diurnal variation in excitation-contraction coupling is lost in the adult spontaneously hypertensive rat heart. J Hypertens 31(6): 1214-1223.

Denniff M, H. E. Turrell HE, et al. (2013). The time-of-day variation in vascular smooth muscle contractility depends on a nitric oxide signalling pathway. J Mol Cell Cardiol 66C: 133-140 

Edroos SA, Vanezis PA, et al. (2012). Remote Ischaemic Conditioning Is Impaired in Diabetes. Heart 98: A61-A61.

Vanezis AP, Edroos SA, et al. (2012). The Inhibitory Effect of Remote Ischaemic Conditioning on a Cellular Model of Cardiac Hypertrophy. Heart 98.

Turrell HE, Rodrigo GC, Norman RI, Dickens M, Standen NB. Phenylephrine preconditioning involves modulation of cardiac sarcolemmal K(ATP) current by PKC delta, AMPK and p38 MAPK. J Mol Cell Cardiol. 2011 Sep;51(3):370-80

Collins HE, Rodrigo GC. Inotropic Response of Cardiac Ventricular Myocytes to beta-Adrenergic Stimulation With Isoproterenol Exhibits Diurnal Variation. Involvement of Nitric Oxide. Circ Res. 2010 Apr 16 106 7 1244-52 


Recent Papers

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