Low-efficiency of percutaneous adenovirus-mediated arterial gene transfer in the atherosclerotic rabbit.

Recombinant adenoviruses are the most efficient vectors with which to perform arterial gene transfer. Previous in vivo studies of adenovirus-mediated arterial transfection, however, have been performed using normal or endothelium-denuded arteries. It is unclear whether these results can be extended to atherosclerotic arteries. Accordingly, this study was designed to (a) assess the feasibility of adenovirus-mediated gene transfer to atherosclerotic lesions, and (b) compare the transfection efficiency, anatomic distribution of transfected cells, and duration of transgene expression achieved in normal versus atherosclerotic arteries. A recombinant adenovirus including a nuclear-targeted beta-galactosidase gene was percutaneously delivered to the iliac artery of normal (n = 25) and atherosclerotic (n = 25) rabbits. Transgene expression, assessed by morphometric as well as chemiluminescent analyses, was documented in all normal and atherosclerotic arteries between 3 and 14 d after gene transfer, but was undetectable at later time points. Transfected cells were identified as smooth muscle cells located in the media of normal arteries, and in the neointima and the vasa-vasora of atherosclerotic arteries. Two percent of medial cells, but only 0.2% of medial and neointimal cells expressed the transgene in normal and atherosclerotic arteries, respectively (P = 0.0001). Similarly, nuclear beta-galactosidase activity was higher in normal than in atherosclerotic arteries (3.2 vs. 0.8 mU/mg protein, P = 0.02). These findings indicate that atherosclerosis reduces the transfection efficiency which can be achieved with adenoviral vectors, and thus constitutes a potential limitation to adenovirus-based, arterial gene therapy.

[Treatment of intrastent restenosis by drug eluting stents: experience from one cardiology centre]. / Traitement des resténoses intrastent par un stent actif: experience monocentrique.

Many interventional treatments have been proposed for intrastent stenosis, in particular by drug-eluting stents, with encouraging results. The aim of this study was to assess the clinical outcome of patients with restenosis of an ordinary uncovered stent treated by a drug eluting stent in a prospective series. The register included 43 patients (50 intrastent restenoses) treated by a drug eluting stent (Cypher or Taxus). The restenosis lesion was focal in 32% of cases with an average length of 14.8 +/- 8 mm and diameter inferior to 2.5 mm in 48% of cases. A Cypher stent was implanted in 44% of cases and a Taxus stent in 56% of cases. After an average follow-up of 6.7 +/- 1.3 months, the major adverse cardiac event rate was 9.3%. It included one transmural infarct in a patient, due to stent thrombosis, and symptomatic restenoses in 3 patients (clinical restenosis rate: 7%). An angiographic control was performed in 15 patients (35%) identifying focal restenosis at the exit of the stent in the 3 symptomatic patients. As in previously reported studies, these results show that with well conducted platelet antiaggregant therapy, the treatment of intrastent restenosis with a drug eluting stent is effective with a low rate of adverse cardiovascular events which compares favourably with previously proposed techniques of management.

Floral induction and determination: where is flowering controlled?

Flowering is controlled by a variety of interrelated mechanisms. In many plants, the environment controls the production of a floral stimulus, which moves from the leaves to the shoot apex. Apices can become committed to the continuous production of flowers after the receipt of sufficient amounts of floral stimulus. However, in some plants, the commitment to continued flower production is evidently caused by a plant's commitment to perpetually produce floral stimulus in the leaves. Ultimately, the induction of flowering leads to the specification of flowers at the shoot apex. In Arabidopsis, floral specification and inflorescence patterning are regulated largely by the interactions between the genes TERMINAL FLOWER, LEAFY and APETALA1/CAULIFLOWER.

Interleukin-10 inhibits intimal hyperplasia after angioplasty or stent implantation in hypercholesterolemic rabbits.

BACKGROUND: Intimal hyperplasia after stent implantation is the main cause of in-stent restenosis. Activated monocytes play a key role in intimal growth. The anti-inflammatory cytokine interleukin-10 (IL-10) is a potent monocyte deactivator, endogenously produced in the atherosclerotic plaque. We tested the hypothesis that exogenous IL-10 may limit postangioplasty intimal hyperplasia after balloon angioplasty or stenting. METHODS AND RESULTS: Hypercholesterolemic rabbits were treated with recombinant human IL-10 (rhuIL-10) for 3 days after balloon angioplasty or 28 days after stent implantation. High IL-10 serum levels and intense deactivation of circulating monocytic cells, assessed by inhibition of IL-1beta release by lipopolysaccharide-stimulated whole blood, were detected for at least 8 hours after rhuIL-10 intravenous injection (ELISA). Morphometric analyses, performed 28 days after injury, indicated that rhuIL-10 reduced intimal growth by approximately 50% after balloon angioplasty or stenting, resulting in more preserved lumen in stented arteries. Moreover, rhuIL-10 reduced macrophage infiltration by 67% and proliferative activity by 81% in the intima and the media. No toxic effect was detected except minor changes in blood cell count. CONCLUSIONS: The anti-inflammatory cytokine rhuIL-10 reduces postinjury intimal hyperplasia. The potent attenuation of in-stent intimal growth by rhuIL-10 and its favorable toxicity profile suggest that rhuIL-10 may be useful in the prevention of in-stent restenosis.

Differential expression of matrix metalloproteinases after stent implantation and balloon angioplasty in the hypercholesterolemic rabbit.

BACKGROUND: Intimal hyperplasia is the principal mechanism of in-stent restenosis. Matrix metalloproteinases (MMPs) play a key role in intimal growth after balloon angioplasty (BA). Little is known, however, about MMP expression after stent implantation (ST). We investigated whether MMP9 and MMP2 are differentially expressed after ST and BA. METHODS AND RESULTS: Hypercholesterolemic rabbits underwent ST and BA in the right and left iliac arteries, respectively. The expression of MMPs and their inhibitors (TIMPs) was studied at various time points in the injured arteries by use of zymography, reverse transcription-polymerase chain reaction, and immunohistochemistry. MMP2, but not MMP9, was constitutively expressed in uninjured arteries. MMP9 expression was rapidly induced after injury, whereas the increase in MMP2 expression was delayed. At all time points, pro-MMP9 activity and MMP9 mRNA levels were >/=2-fold (ANOVA, P=0.002) and >/=3-fold (P<0.0001) higher after ST than after BA, respectively. Active MMP9 was detected only after ST. Although the increases in MMP2 mRNA levels were of similar magnitudes after ST and BA, pro-MMP2 activity was slightly higher 7 and 30 days after ST, and MMP2 activity was >/=2-fold higher 7 to 60 days after ST (P=0.002). No difference in TIMP expression was observed between stented and balloon-injured arteries. Cellular distributions of MMPs and TIMP1 were similar after ST and BA. Early inflammatory cell recruitment and 30-day intimal growth were more severe after ST. CONCLUSIONS: Stent implantation results in more intense and sustained expression of MMP9 and activation of MMP2 than balloon angioplasty.

Gene therapy for the vulnerable plaque.

Acute coronary events result from the rupture of an atherosclerotic plaque, leading to formation of an occlusive coronary thrombus. Recent developments in the field of gene transfer provide the opportunity to genetically modify cells involved in plaque rupture as well as thrombus formation and thus prevent acute coronary syndromes. A first approach consists of transferring genes, the product of which may stabilize the vulnerable plaque by reducing the plaque content in lipids and macrophages. Alternatively, the introduction into the atherosclerotic plaque of genes encoding for thrombolytic proteins or growth factors able to restore physiologic antithrombotic functions of endothelial cells may inhibit thrombus formation should the plaque rupture. The success of such strategies depends on the efficiency with which the transgene is introduced and expressed into the target cell, the duration of transgene expression and the ability of the transgene product to ultimately prevent plaque rupture or thrombus formation, or both.

Reperfusion syndrome: relationship of coronary blood flow reserve to left ventricular function and infarct size.

OBJECTIVES: We tested the hypothesis that the reperfusion syndrome (RS), defined as an additional elevation of the ST segment upon reperfusion, may be a marker of microcirculatory reperfusion injury during acute myocardial infarction (AMI). BACKGROUND: The pathophysiology of the RS is unknown, and its prognostic implications are controversial. METHODS: Twenty-one patients with an anterior AMI treated < or =12 h after onset by primary coronary angioplasty (PTCA) were studied. Coronary velocity reserve (CVR), an index of microcirculatory function, was measured using a Doppler guidewire. Left ventricular (LV) ejection fraction, infarct size (percent defect) and LV end-systolic volume index (LVESVi) were evaluated by radionuclide ventriculography, 201T1 single-photon emission computed tomography and contrast ventriculography, respectively. RESULTS: Baseline ST elevation and pain-to-TIMI 3 time were similar in patients with and without RS. Patients with RS (10/21) had a lower post-PTCA CVR than patients without RS (median [95% confidence interval]: 1.2 [1-1.3] vs. 1.6 [1.5-1.7], p < 0.005). Even though predischarge CVR was similar in the two groups, infarct size at six weeks (26 [21 to 37] vs. 14 [10-17]% 201T1 defect, p = 0.001) and predischarge LVESVi (45% [40 to 52] vs. 30% [29 to 38] mL/m2, p = 0.001) were larger, and LV ejection fraction at six weeks (40% [37 to 46] vs. 55% [50 to 60], p = 0.004) was lower in patients with RS than in patients without RS. CONCLUSIONS: Patients with RS during primary PTCA for an anterior AMI have a transiently lower CVR than patients without RS, but sustained LV dysfunction and larger infarct size, suggesting that RS is a marker of microcirculatory reperfusion injury.

The French Randomized Optimal Stenting Trial: a prospective evaluation of provisional stenting guided by coronary velocity reserve and quantitative coronary angiography. F.R.O.S.T. Study Group.

OBJECTIVES: We sought to make a prospective comparison of systematic stenting with provisional stenting guided by Doppler measurements of coronary velocity reserve and quantitative coronary angiography. BACKGROUND: Despite the increasing use of stents during percutaneous transluminal coronary angioplasty, it is unclear whether systematic stenting is superior to a strategy of provisional stenting in which stents are placed only in patients with unsatisfactory results or as a bail-out procedure. METHODS: Two hundred fifty-one patients undergoing elective coronary angioplasty were randomly assigned either to provisional stenting (group 1, in which stenting was performed if postangioplasty coronary velocity reserve was <2.2 and/or residual stenosis > or =35% or as bail-out) or to systematic stenting (group 2). The primary end point was the six-month angiographic minimal lumen diameter (MLD). Major adverse cardiac events were secondary end points (death, acute myocardial infarction and target lesion revascularization). RESULTS: Stenting was performed in 48.4% of patients in group 1 and 100% of patients in group 2 (p<0.01). Six months after angioplasty, the MLD did not differ between groups (1.90+/-0.79 mm vs. 1.99+/-0.70 mm, p = 0.39), as was the rate of binary restenosis (27.1% vs. 21.4%, p = 0.37). Among patients with restenosis, 13/32 (40.6%) in group 1 but 100% (25/25) in group 2 had in-stent restenosis (p<0.01). Target lesion revascularization (15.1% vs. 14.4% in groups 1 and 2 respectively, p = 0.89) and major adverse cardiac events (15.1% vs. 16.0%, p = 0.85) were not significantly different. CONCLUSIONS: Systematic stenting does not provide superior angiographic results at six months as compared with provisional stenting.

Optimal techniques for arterial gene transfer.

Cardiovascular gene therapy is becoming a clinical reality due to improved vectors, delivery systems and careful experimental validation studies. Nearly all cardiovascular diseases are amenable to gene therapy, but the optimal combination of vector, delivery system and therapeutic gene is likely to be unique to each application. Currently, the most efficient vectors available are replication-defective adenoviral vectors, but transgene expression is limited in time due to a strong immune response. Conversely, non-viral vectors or plasmid DNA may be used safely but have very limited efficiency. Percutaneous, catheter-based delivery is feasible for most applications. The ultimate issues that will decide of the future of gene therapy are safety of the transfer and delivery techniques as well as cost/effectiveness comparisons with alternative therapies, including local delivery of drugs, proteins and/or mechanical devices.

Perspectives of arterial gene therapy for the prevention of restenosis.

Restenosis remains the main limitation of interventional cardiology. Restenosis is an important target for gene therapy since it is frequent (30% of patients), costly (estimated $2 billion annually), refractory to all pharmacological therapies, and related, at least in part, to smooth muscle cell proliferation which is an inviting target for antiproliferative molecular strategies. Because cell division is ultimately controlled by intranuclear events, the protein product of genes selected for their antiproliferative effects usually remains inside the cells. Consequently, the transfer of growth-inhibitory genes needs to be efficient-i.e., involve a large proportion of smooth muscle cells populating the angioplasty site. To date, adenoviral vectors are, by far, the most efficient vectors to perform in vivo arterial gene delivery. These vectors, as well as others, have been recently used to demonstrate that therapeutic genes encoding cytolytic (thymidine kinase) or cytostatic (hypophosphorylatable retinoblastoma protein, endothelial nitric oxide synthase, gax, etc.) products successfully inhibit smooth muscle cell proliferation and related intimal hyperplasia. Despite substantial progress, major technical issues remain to be addressed before gene therapy is applied to clinical restenosis. First-generation recombinant adenoviruses evoke both cellular and humoral immune responses leading to local toxicity and transient gene expression. Moreover, the low efficiency of gene transfer to atherosclerotic arteries may further impair the biological effect of antiproliferative genes. Finally, restenosis is a multifactorial phenomenon in which intimal hyperplasia plays an important but not exclusive role. Prevention of constrictive remodeling should also be taken into account in an integrated genetic strategy to prevent restenosis.

The Dispatch catheter as a delivery tool for arterial gene transfer.

OBJECTIVE: Most currently available percutaneous delivery methods for arterial gene therapy are limited by the need for a long incubation period, which may lead to unacceptable tissue ischemia, especially in the coronary vasculature. Conversely, shorter incubation times may result in inefficient gene transfer, especially in atheromatous arteries. A new local delivery autoperfusion multichamber catheter is now available which permits local delivery in the coronary arterial system without inducing myocardial ischemia. The present study aimed at evaluating the performance of this catheter for achieving arterial gene transfer using replication-defective adenoviral vectors in normal and atheromatous arteries. METHODS: A replication-defective adenoviral vector carrying a nuclear-targeted beta-galactosidase reporter gene (Ad-RSV beta gal, 5.10(9) plaque-forming units [pfu]) was delivered to the iliac arteries of normal (n = 7) and atheromatous (1% cholesterol diet + arterial abrasion) (n = 6) rabbits, via a multichamber autoperfusion balloon catheter (Dispatch, SciMed). Duration of gene delivery was 60 min. RESULTS: Three days later, marked expression of the reporter gene was detected by histochemistry in the endothelium at the delivery site (percentage of transfected cells: 16 +/- 8% / artery (range 11-25%). There was a low transduction rate in medial smooth muscle cells 0.7 +/- 0.4%/artery (range 0.3-1.1%). In atheromatous arteries, transduction was consistently achieved in the superficial layers of the neointima but was lower (1.1 +/- 0.5%/artery, range 0.3-1.7%). Transgene expression was detected by histochemistry in the liver of 3/13 animals, suggesting that there is a substantial risk of systemic dissemination of the viral vectors. CONCLUSION: Efficient arterial gene delivery to endothelial and superficial smooth muscle cells is feasible using local delivery of adenoviral vectors via the Dispatch autoperfusion catheter, in both normal and atheromatous arteries. This perfusion catheter may be a useful tool for coronary artery gene transfer.

Effects of interleukin-10 on monocyte/endothelial cell adhesion and MMP-9/TIMP-1 secretion.

OBJECTIVE: Monocyte adhesion to endothelial cells and subsequent secretion of matrix metalloproteinases (MMPs) by activated macrophages are key events in arteriosclerosis and restenosis. We tested the hypothesis that interleukin-10 (IL-10), a potent anti-inflammatory cytokine, inhibits monocyte-endothelial cell interactions. METHODS: The effect of IL-10 on monocyte/endothelial cell adhesion, as well as on the expression of MMP-9 and the tissue inhibitor of MMP-9, TIMP-1, were first tested in vitro in coculture systems. In addition, we used an ex vivo binding assay to study the inhibitory effect of IL-10 on monocyte adhesion to carotid arteries obtained from either normal, or L-nitro arginine-methyl ester (L-NAME)-treated rats. The effect of IL-10 on the expression of monocyte adhesion molecules (CD18 and CD62-L) was studied by flow cytometry. RESULTS: IL-10 (150 ng/ml) inhibits monocyte adhesion to endothelial cells (by 35%) and to carotid arteries (by 40 and 50%, in normal and L-NAME-treated rats, respectively), via direct modulation of the expression of CD18 and CD62-L. Moreover, IL-10 dose-dependently decreases MMP-9 activity and increases TIMP-1 levels in coculture systems, both at the transcriptional level. CONCLUSIONS: Our results suggest that IL-10 is an important modulator of monocyte-endothelial cell interactions.

Effects of poloxamer 407 on transfection time and percutaneous adenovirus-mediated gene transfer in native and stented vessels.

UNLABELLED: Reduction in transfection time and the ability to perform gene transfer in conjunction with endovascular stent implantation constitute two important challenges for percutaneous adenovirus-mediated gene transfer to vessel walls. Studies have suggested that the use of biocompatible polyol poloxamer 407 could be useful. We first evaluated the use of poloxamer 407 for percutaneous gene transfer in nonstented rabbit iliac arteries. A 200-microl mixture of Ad-RSVbetagal or Ad-CMVLuc in either phosphate-buffered saline (PBS) or 20% poloxamer was delivered. After 3 days, gene transfection was evaluated by X-Gal staining or measurement of luciferase activity. Poloxamer use resulted in a 3- to 15-fold increase in the percentage of transfected cells (X-Gal, p = 0.001) and a 16-fold increase in protein product (luciferase activity, p = 0.03), and allowed a decrease in transfection time from 30 to 5 min with minimal reduction in transfection efficiency. We then evaluated the feasibility of percutaneous gene transfer, using Ad-RSVbetagal diluted in pure PBS or 20% poloxamer, in conjunction with stent implantation. Gene delivery was performed either immediately before (pre-) or after (post-) stent implantation. When adenoviruses were diluted in PBS, gene transfer had a low efficiency (prestent, 0.3%; poststent, 0.2%; NS). With poloxamer, the efficacy was much higher (p = 0.0001) and similar "pre" (2.2%) or "post" (1.7%) stent delivery (NS). CONCLUSIONS: (1) The use of poloxamer, rather than PBS, as a vehicle increases the efficacy of percutaneous adenovirus-mediated gene transfer and reduces transfection time; (2) gene transfer performed during stent implantation with poloxamer is feasible and achieves a significant level of gene expression. Thus percutaneous gene delivery is applicable to conventional stents and could present an attractive method by which to achieve local biological effects in a stent environment.

Relationship between resting 201Tl reverse redistribution, microvascular perfusion, and functional recovery in acute myocardial infarction.

UNLABELLED: 201TI reverse redistribution is a common finding early after reperfusion therapy for myocardial infarction. Its mechanism and clinical implications remain unclear. The aim of this study was to clarify the relationships between reverse redistribution, microvascular perfusion, and myocardial viability. METHODS: Resting, 10-min-postinjection, and redistribution 201TI data obtained for 33 patients 8 and 42 d after the onset of acute myocardial infarction were compared with echocardiographic wall motion measured acutely and on day 42. Microvascular perfusion was assessed by myocardial contrast echocardiography performed 10 min after restoration of complete patency of the infarct artery. RESULTS: Marked significant reverse redistribution was found on day 8 (absolute change, 7.5%+/-7.9% of the 10-min-postinjection defect size; P<5x0.000001) and significantly decreased on day 42 (2.7%+/-6.8%; P = 0.004 between days 8 and 42). The 10-min-postinjection defect size best predicted the final infarct size on day 42 and was closely related to microvascular perfusion. Patients with adequate reperfusion had a smaller postinjection defect on day 8 (21.1%+/-14.6%) and a larger reverse redistribution (10.2%+/-6.1%) than did patients with no reflow (35.3%+/-13% and 3.2%+/-9.2%, respectively; P<0.04 for both). CONCLUSION: Reverse redistribution was marked early after myocardial infarction in patients with complete patency of the infarct artery and decreased in subsequent weeks. Reverse redistribution was associated with restoration of adequate microvascular reperfusion and with myocardial salvage and viability. The early postinjection scans on day 8 were the relevant images for assessing myocardial salvage and predicting wall motion recovery.

Heterogeneity of prognosis in patient subsets treated by primary coronary angioplasty during acute myocardial infarction.

Among 377 patients consecutively treated with primary coronary angioplasty for acute myocardial infarction, in-hospital mortality was higher in patients ineligible than in patients eligible for thrombolysis (14.4% vs 7.8%, p <0.05). It remained dismal (75.9%) in patients with cardiogenic shock, but was similar in lytic-eligible patients and in those who were ineligible because of an increased bleeding risk (7.8% vs 7.2%, p = NS), and was zero in patients with nondiagnostic electrocardiograms.

Modulation of the expression of the granulocyte adhesion molecule, CR3, by percutaneous transluminal coronary angioplasty and contrast media.

RATIONALE AND OBJECTIVES: The effects of percutaneous transluminal coronary angioplasty (PTCA) and iodinated contrast media on the functional state of polymorphonuclear leukocytes (PMN) were determined; the expression of the PMN adhesion molecule, CR3, was assessed. METHODS: CR3 expression was measured by flow cytometry in whole blood samples in vivo, before and after PTCA (n = 17) or coronary angiography (n = 16); and in vitro, before and after incubation of PMNs with iodinated contrast media (n = 5). RESULTS: CR3 expression (mean +/- standard error of the mean, arbitrary units) decreased significantly after PTCA (221 +/- 25 to 168 +/- 21, P < .005) and coronary angiography (297 +/- 43 to 218 +/- 25, P < .05). In vitro, there was a dose-dependent decrease of CR3 expression and a significant and strong inverse correlation between CR3 expression and the contrast agent concentrations regardless of the type of contrast agent used. CONCLUSIONS: These data suggest that PTCA does not activate circulating PMNs, and that contrast media decrease CR3 expression. Whether this is related to the systemic adverse effects of contrast media remains to be clarified.

The habits of roots: what's up down under?

NASA: Defining interactions of roots with the surrounding soil environment has been the focus of many recent investigations. As a result of these efforts, we are gaining an appreciation of the varied and often surprising strategies whereby roots adjust to and condition their soil environment for optimal growth and development. This article summarizes current knowledge of the often complex interactions between roots and biotic and abiotic factors within the soil. These interactions are interpreted in terms of modifications in the development or the physiology of the root.^ieng

Prevention of restenosis after coronary angioplasty: towards a molecular approach?

Restenosis after coronary angioplasty, the main limitation of interventional cardiology, remains an unsolved issue. The failure to-date of all pharmacological attempts at prevention has prompted the development of alternative strategies. A mechanistic approach to the problem of restenosis is based on the assumption that creating a more satisfactory acute angioplasty result would reduce the development of restenosis. With the exception of coronary stenting, however, none of the new angioplasty devices have convincingly reached this goal. Furthermore, recent advances in the field of vascular biology have opened new avenues for a molecular approach of restenosis. Better understanding of the pathophysiology of restenosis, in conjunction with high-pace development of catheter, polymer, and virus technologies, provide opportunities to deliver agents--drugs, genes, or antisense oligonucleotides--locally, at the site of angioplasty to interfere specifically with the restenosis process. Some of these molecular strategies are currently being investigated in animal models. Clinical application of a molecular approach to prevent restenosis, however, will require close collaboration between physicians, molecular biologists, and bio-engineers.

Clinical criteria for identifying early oral and oropharyngeal carcinoma: erythroplasia revisited.

From 1961 to 1981, we evaluated 502 asymptomatic oral and oropharyngeal lesions in a veterans population of tobacco and alcohol users. Three hundred twenty-six cancers (236 invasive and 90 in situ) in 276 patients were recorded and described. For invasive cancers and in situ lesions, 64 percent and 54 percent, respectively, were red or predominantly red. Eleven percent and 16 percent were white only or predominantly white. The invasive cancers were more often granular than the in situ cancers. The traditional clinical characteristics of ulceration, induration (palpability), elevation, bleeding, and associated cervical adenopathy were not usually present in these early lesions. We found leukoplakia to be a variable characteristic as opposed to the almost constant presence of erythroplasia. These findings strongly suggest that it would probably be useful to eliminate the term leukoplakia from the discussion of cancer in a population of tobacco and alcohol users.

Inhibitory effects of KN-93, an inhibitor of Ca2+ calmodulin-dependent protein kinase II, on light-regulated root gravitropism in maize.

Light is essential for root gravitropism in Zea mays L., cultivar Merit. It is hypothesized that calcium mediates this light-regulated response. KN-93, an inhibitor of calcium/calmodulin kinase II (CaMK II), inhibits light-regulated root gravitropism but does not affect light perception. We hypothesize that CaMK II, or a homologue, operates late in the light/gravity signal transduction chain. Here we provide evidence suggesting a possible physiological involvement of CaMK II in root gravitropism in plants.